Optical probe having and methods for difuse and uniform light irradiation

ABSTRACT

A variety of optical probes and methods have utility in the examination of various materials, especially materials in the interior of cavities having restricted access through orifices or passageways. One type of such optical probe is elongated and includes a distal optical window, a divergent light source, a spatial mixer, and a light collector. Light from the light source is mixed in the spatial mixer to achieve uniform diffuse light in the vicinity of the optical window. The light collector receives light from the target through the spatial mixer. The optical probe may be made of two sections, a reusable section and a disposable. The disposable is elongated and contains a mounting section, an inside surface suitable for the spatial mixing of light, and an optical element which helps to seal the reusable probe section from the target.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of and claims thebenefit of U.S. patent application Ser. No. 09/111,174, filed Jul. 8,1998 (Deckert et al., “Optical Probe Having and Methods for UniformLight Irradiation and/or Light Collection Over a Volume”), which ishereby incorporated herein in its entirety by reference thereto.

BACKGROUND OF THE INVENTION

[0002] 1. Field of the Invention

[0003] The present invention relates to optical probes and opticalmethods, some embodiments thereof being particularly related to opticalprobes and methods having utility in the examination of material,especially material in the interior of cavities having restricted accessthrough orifices or passageways, and some embodiments thereof beingparticularly related to optical probes and methods having utility in theexamination of the epithelia and other tissues of anatomical structureswithin the body cavities and tubular organs and viscera of mammals.

[0004] 2. Description of Related Art

[0005] Various apparatus are known for optically probing the interior ofcavities of living and non-living bodies. An early inspection apparatusthat uses a disposable sheath and which has particular application tothe human cervix is described in U.S. Pat. No. 3,945,371 entitled“Apparatus for Inspection and Sampling in Restricted Aperture CavitiesEmploying Fibre Optics,” issued Mar. 23, 1976 to Adelman. The disposablesheath has an upper duct terminating in a protective window forcontaining either one fiber optic bundle or two fiber optic bundles usedin illuminating tissue and collecting a reflected image from the tissue.The light source is a lamp mounted in a reflector that concentrates thelight on the end of the fiber optic bundle being used for illumination.By selecting the numerical aperture, or NA, of the fiber materials usedin the image collecting fiber optics bundle, different capabilities areachieved. Fiber materials having an NA of 0.56 permit close inspectionof the tissues at a viewing distance of 3 mm with low illumination,while fiber materials having an NA of 0.099 permit a general vantage ata viewing distance of 2 cm with high illumination. The possibility ofusing lenses is mentioned but not elaborated on.

[0006] More recently, an optical probe for use in the diagnosis of thetissues of the human cervix using fluorescence and Raman spectroscopieshas been described in U.S. Pat. No. 5,697,373 entitled “Optical Methodand Apparatus for the Diagnosis of Cervical Precancers using Raman andFluorescence Spectroscopies,” issued Dec. 16, 1997 to Richards-Kortum etal. The probe, which includes 2 excitation fibers and 5 collectionfibers, is a type know as “multi-point contact” because it uses discretecollection fibers disposed a substantially fixed distance from thetissue surface to detect fluorescence and/or Raman emissions from tissueregions proximate the distal fiber ends. The fixed distance ismaintained by a quartz shield or window which contacts the tissue underinvestigation. The probe is part of a diagnostic or screening systemthat includes electromagnetic sources for generating the excitationenergy, filters or spectrum analyzers for isolating wavelengths ofinterest, and computers for processing the wavelengths of interest todetermine the tissue properties of interest. Another optical probe usinga large number of paired excitation/collection fibers and a shapedcontact window is described in U.S. Pat. No. 5,699,795 entitled “OpticalProbe for the Detection of Cervical Neoplasia Using FluorescenceSpectroscopy and Apparatus Incorporating Same,” issued Dec. 23, 1997 toRichards-Kortum et al. One embodiment uses 31 fiber optic pairs in abundle while another embodiment uses 357 fiber optic pairs in a bundle.

[0007] One disadvantage of the multi-point contact probe is its shallowdepth of field, which generally necessitates that the ends of thecollection fibers in the distal end of the probe be positioned a shortfixed distance from the target. If any portion of the distal end of thecontact probe were not properly positioned, the light energy returningfrom the target would not be accurately detected due to the criticaldepth-of-field properties of such a probe. Improper positioning of acontact probe can result from operator error or from a target that isangled with respect to the contact probe's distal end to such an extentthat full contact cannot be achieved. Another disadvantage of themulti-point contact probe is its limited resolution, which is apractical result of the difficulty and expense of assembling a largenumber of very fine fibers into a small probe. Yet another disadvantageof the multi-point contact probe is the lack of uniform excitation andcollection of emissions due to the necessary spacing-apart of theexcitation fibers and the collection fibers at the distal end of theprobe.

[0008] Optical devices using lenses avoid some of the disadvantages ofpoint contact optical probes in that they typically have betterdepth-of-field and better resolution. However, achieving uniform lightillumination has remained problematic. Many endoscopes have offsetilluminating and observing optical systems and suffer unevenillumination produced by the parallax inherent in the offsetarrangement. Some endoscopes have coaxially arranged illuminating andobserving optical systems to eliminate the non-uniformity introduced byparallax. For example, European Patent Specification number 0 343 558B1, published Oct. 12, 1994 and entitled “Image Picking-Up andProcessing Apparatus” describes an endoscope having an optical fiberbundle arranged such that its end surface surrounds an objective lensused to detect reflected light. However, the illumination achieved bythis ring of discrete optical fibers is not uniform. Another type ofendoscope described in U.S. Pat. No. 4,671,630 entitled “IlluminatingOptical System for Endoscopes,” which issued Jun. 9, 1987 to Takahashi,also has coaxially arranged illuminating and observing optical systemsto eliminate the non-uniform illumination introduced by parallax. Toovercome the non-uniformity of earlier coaxially-arranged illuminatingand observing optical systems, Takahashi uses a rectangularparallelopipedal transparent body or prism in front of the objectivelens of the observing optical system and introduces light from the sideof the prism. Except where the illumination enters, the sides of theprism are reflecting surfaces. Illumination light introduced into theprism is totally reflected on the objective surface due to thedifference in the refractive indices of the prism and air and is alsototally reflected by the reflecting side surfaces of the prism, butprojects out of the object surface due to the higher refractive index ofwater relative to air in the tissue against which the prism is pressedduring normal use. The object surface is thereby directionallyilluminated, nearly obliquely so, which exaggerates shadows fromirregularities in the tissue and permits a strong stereoscopic image tobe achieved. While this type of illumination may be useful forobservation by reflected light, its usefulness for observations based onlight interactions with tissue other than reflectance is not described.Another type of endoscope described in U.S. Pat. No. 5,700,236 entitled“Endoscope Attachment for Changing Angle of View,” which issued Dec. 23,1997 to Sauer et al., uses a sheath having a distal portion thatcontains structure for changing the angle of view and/or illuminationangle of an endoscope. Structure for changing the view angle include aprism, and structure for changing the illumination angle include aprism, a curved light guide, and an angled optical fiber. However, theillumination achieved by the discrete optical fibers is not uniform fortypical light interaction analysis. No measures are described forachieving uniform light using the alternative techniques.

SUMMARY OF THE INVENTION

[0009] A need, therefore, exists for apparatus and methods of providinguniform irradiation for observation involving light interactions withtissue other than reflectance or in addition to reflectance. Forexample, while diagonal illumination as described in the aforementionedTakahashi patent may be suitable for use with optical systems thatobserve reflected light, it is not effective for use with opticalsystems that are designed to observe light coming from within a target.For example, the aforementioned Richards-Kortum '373 patent describessystems based on cell fluorescence and/or Raman scattered light, both ofwhich are attributable to light that emanates from within tissue cellsand not light reflected from the tissue surface. Optical systems havingparallax or producing non-uniform or highly angled light relative to thetarget surface are not optimal for fluorescence and Raman -basedsystems, which require uniform diffuse light irradiation capable ofpenetrating into the target for quantitative or qualitative analysis.

[0010] Accordingly, an object of the present invention in various of itsembodiments is to front-irradiate target materials with light that isuniform and diffuse with many near-normal rays relative to the generalorientation of the target surface, throughout a field of view of thelight detection system.

[0011] Another object of the present invention, in various of itsembodiments, is to provide an irradiation system that uses a separateoptical probe section, whether reusable, disposable, or single use, tocontact target materials. Some components of the irradiation system areincorporated into the separate section of the optical probe while othercomponents of the light delivery system are incorporated into a reusablesection of the optical probe.

[0012]

[0013] Another object of the present invention, in various of itsembodiments, is to incorporate only low cost components of anirradiation system into a disposable or single-use section of theoptical probe, while other components of the irradiation system,including high cost components, are incorporated into the reusablesection of the optical probe.

[0014] These and other objects are achieved in various embodiments ofthe present invention. One embodiment of the present invention is anoptical probe having a distally disposed optical window, comprising alight collector, a light source, and a spatial mixer. The lightcollector has an axis of light collection passing through the opticalwindow and a focal plane generally proximate the optical window. Thelight source has a light projection pattern about the axis of lightcollection. The spatial mixer has a proximal end in opticalcommunication with the light source, a distal end in opticalcommunication with the optical window, and an axis of light projectionpassing through the optical window. The spatial mixer also has a lightmixing surface that is partially intersected by the light projectionpattern of the light source to establish a distribution of irradiationray angles proximate the optical window that has a maximum away fromnormal and near-normal to the axis of light projection. In a variationthereof, the light mixing surface is partially intersected by the lightprojection pattern of the light source to establish a distribution ofirradiation ray angles proximate the optical window that has a maximumnear-parallel to the axis of light projection.

[0015] Another embodiment of the present invention is an optical probefor examining, through an optical window therein, living tissue in theinterior of cavities having restricted access through orifices orpassageways, comprising a body, a lens system, a light source, and anelongated inside surface. The body has an elongated distal sectioncontaining the optical window, and a proximal section. The lens systemis mounted in the body and has an optical axis passing through theoptical window of the probe and a focal plane lying generally proximateto the optical window. The light source is mounted in the body about thelens system and is coaxial with the lens system with a direction oflight projection generally toward the optical window. The elongatedinside surface has one end disposed generally about the light source andanother end disposed generally about the optical window, the insidesurface comprising a light scattering surface and the light projectionat least partially intersecting the light scattering surface toestablish a distribution of ray angles proximate the optical window thathas a maximum near-parallel to the optical axis of the lens system.

[0016] A further embodiment of the present invention is an optical probehaving a distally disposed optical window and comprising a lightcollector, a light source, and a spatial mixer. The light collector hasan axis of light collection passing through the optical window and afocal plane generally proximate the optical window. The light source hasa plurality of light emitting areas disposed about the axis of lightcollection. The spatial mixer has a proximal end in opticalcommunication with the light source and a distal end in opticalcommunication with the optical window to establish a direction of lightprojection generally toward the optical window and generally along atleast part of the axis of light collection, the spatial mixer furtherhaving a light mixing surface at least partially intersected by rays oflight from the light emitting areas to establish a diffuse lightproximate the optical window having a distribution of irradiation rayangles that has a maximum away from normal and near-normal to thedirection of light projection. In yet a further embodiment, the rays oflight from the light source that intersect the light mixing surfaceestablish, along with direct rays of light from the light source, adiffuse light proximate the optical window having a distribution of rayangles that has a maximum near-parallel to the direction of lightprojection.

[0017] Yet another embodiment of the present invention is a disposablefor an optical probe, the disposable having a distal end to contact atarget having a fluid associated therewith and a proximal end to mountto a reusable optical probe section. The disposable comprises a bodyhaving a mounting surface toward the proximal end and a light mixinginside surface toward the distal end, and an optical window elementdisposed within the body. The optical window element and the bodyproximal of the optical window element are barriers to the fluid.

[0018] Another embodiment of the present invention is a disposable foran optical probe, the disposable having a distal end to contact a targethaving a fluid associated therewith and a proximal end to mount to areusable optical probe section, the disposable comprising a body, anoptical element, and a reusable optical probe section connector. Thebody has an inside surface bounding an interior space extending betweenthe proximal end and the distal end, the inside surface comprising atleast in part a light mixing surface. The optical element is disposedacross the interior space, the optical element and the body at leastproximal of the optical element being barriers to the fluid. Thereusable optical probe section connector is integrated with the body.

[0019] Another embodiment of the present invention is a disposable foran optical probe, the disposable having a distal end to contact a targethaving a fluid associated therewith and a proximal end to mount to areusable optical probe section, the disposable comprising a tubularplastic body, an optical element, and a reusable optical probe sectionconnector. The tubular plastic body has an inside surface bounding aninterior space extending between the proximal end and the distal end,the inside surface comprising at least in part a light mixing surface.The optical element is disposed across the interior space, the opticalelement and the body being barriers to the fluid. The reusable opticalprobe section connector is integrated with the body.

BRIEF DESCRIPTION OF THE DRAWINGS

[0020]FIG. 1 shows schematically the basic elements of an illustrativesystem for the optical examination of materials.

[0021]FIG. 2 shows schematically the principal elements of an opticalprobe that is suitable for use with the system of FIG. 1 to probematerial in the interior of cavities having restricted access throughorifices or passageways for other means of examination.

[0022]FIG. 3 is a plan cutaway side view of an optical probeillustrating basic elements of an irradiation system, the probe beingsuitable for viewing, analyzing and/or treating material in the interiorof cavities having restricted access through orifices or passageways.

[0023]FIG. 4 is a cross-section of the optical probe of FIG. 3 takennormal to the optical axis thereof near a ring light source within theirradiation system, which illustrates in cross-section the output of thering radiation source.

[0024]FIG. 5 is a cross-section of the optical probe of FIG. 3 takenalong the optical axis thereof and through the irradiation optical path,the collection optical path, and a spatial mixer contained therein, andwhich shows the behavior of various exemplary rays in the irradiationpath.

[0025]FIG. 6 is a plan side cutaway view of the optical probe of FIG. 3illustrating basic elements of a radiation collection system along withsome elements of the irradiation system.

[0026]FIG. 7 is a plan side cutaway view of an optical probe like theoptical probe of FIG. 6 but illustrating alternative elements of aradiation collection system along with some elements of the irradiationsystem.

[0027]FIG. 8 is a ray trace diagram showing how reflected radiation raysfrom an intermediate window are blocked in a collection system with anaperture.

[0028]FIG. 9 is a side view of an optical probe showing the relationshipbetween a reusable section and a disposable section thereof.

[0029]FIG. 10 is a plan cutaway side view of the reusable optical probesection of FIG. 9 that shows portions of an irradiation system and aradiation collection system, the probe being suitable for use inviewing, analyzing and/or treating material in the interior of cavitieshaving restricted access through orifices or passageways.

[0030]FIG. 11 is a plan cutaway side view of an alternative reusableoptical probe section that shows portions of an irradiation system and aradiation collection system, the probe being suitable for use inviewing, analyzing and/or treating material in the interior of cavitieshaving restricted access through orifices or passageways.

[0031] FIGS. 12-19 are views of various alternative light or radiationguide components for the optical probes of FIGS. 10 and 11, includingcross-section views along the optical axes thereof and corresponding endviews.

[0032]FIG. 20 is a plan cutaway side view of an optical probe that showsportions of an irradiation system using light guides and a radiationcollection system, the probe having a reusable section and a disposablesection and being suitable for use in viewing, analyzing and/or treatingmaterial in the interior of cavities having restricted access throughorifices or passageways.

[0033]FIG. 21 is a plan cutaway side view of an illustrative mountingassembly through which light is introduced into liquid light guides.

[0034]FIG. 22 is a sectional view of the mounting assembly of FIG. 21.

[0035]FIG. 23 is a sectional view through the optical probe of FIG. 20showing a technique for retaining light guides therein.

[0036] FIGS. 24-27 are cross-sections through various disposable probesections suitable for use with the reusable probe section shown in FIGS.10 and 11.

[0037]FIG. 28 is a cross-section view of a disposable that is suitablefor use with the reusable probe section shown in FIG. 20 and whichincludes extruded components.

[0038]FIG. 29 is a exploded cross-section view of a joint contained inthe disposable shown in FIG. 28.

[0039]FIG. 30 is a cross-section view of a disposable that is suitablefor use with the reusable probe section shown in FIG. 20 and whichincludes molded components.

[0040]FIG. 31 is a side view of an optical probe showing therelationship between a reusable section and a disposable sectionthereof.

DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED EMBODIMENTTHEREOF

[0041]FIG. 1 shows schematically the basic elements of an illustrativeoptical system for the examination of materials. As used herein, opticsrefers to the branch of physics that deals with the generation,propagation, and detection of electromagnetic radiation havingwavelengths greater than x-rays and shorter than microwaves, and lightrefers to electromagnetic radiation at one or more wavelengths(narrowband, broadband, or any combination thereof) anywhere in theelectromagnetic spectrum greater than x-rays and shorter thanmicrowaves. An optical probe 130 is used to irradiate the material beingexamined (i.e. the target) and for collecting radiation from the targetdue to the irradiation. A system controller and processor 100 controlsthe various operations performed by the system and processes variouscharacteristics of the radiation image collected from the target toobtain multispectral indications about various properties of the targetmaterial. Where the material is mammalian tissue which may suffer one ormore abnormalities, the system controller and processor 100 may useappropriate algorithms to determine whether the tissue is normal orabnormal, including the type of abnormality, and display the result; oruse appropriate algorithms to calculate a probability of the tissuebeing normal or abnormal and, if abnormal, a probability of the type ofabnormality, and display the result; or use appropriate algorithms toscreen the tissue for abnormality and display the result; or control thepower, duration, and other characteristics of light projected onto thetissue for treating tissue abnormality; or a combination of theforegoing. A light engine 110 includes one or more electromagneticenergy sources for generating specific irradiation wavelengths. A lightdetector 120 includes such components as filters and detectors or aspectrum analyzer for measuring the amplitude of wavelengths of interestin the probe image over the field of view of the probe 130. The systemcontroller and processor 100 is coupled to the light engine 110 andlight detector 120 to control the various operations thereof. The lightengine 110 and light detector 120 are coupled to the optical probe 130using any suitable means such as fiber optic cable, although othercoupling techniques such as liquid light guides may be used instead. Ifdesired, various of the components of the light engine 110, the lightdetector 120, or both may be integrated into the probe 130, in whichcase various hardwired or wireless techniques may be used to couple thesystem controller and processor 100 to the probe 130. If the probe 130contains any controllable or powered components, the probe 130 may beconnected to the system controller and processor 100 to receive controlsignals and/or power and/or furnish status signals. Examples of systemsfor the optical examination of mammalian epithelial tissues include U.S.Pat. No. 5,697,373 entitled “Optical Method and Apparatus for theDiagnosis of Cervical Precancers using Raman and FluorescenceSpectroscopies,” issued Dec. 16, 1997 to Richards-Kortum et al., andU.S. patent application Ser. No. 08/666,021 entitled “Diagnostic Methodand Apparatus for Cervical Squamous Intraepithelial Lesions in Vitro andin Vivo Using Fluorescence Spectroscopy,” filed Jun. 19, 1996 in thename of Richards-Kortum et al., which hereby are incorporated herein intheir entirety by reference thereto.

[0042]FIG. 2 shows schematically the principal elements of an opticalprobe 200 that is suitable for use in the system of FIG. 1 to probematerial in the interior of cavities having restricted access throughorifices or passageways, such as, in the case of mammals, the epitheliaand anatomical structures within their body cavities, and tubular organsand viscera. For access to tissue within generally tubular cavities, theprobe 200 preferably is elongated and generally cylindrical (includinground, oval, and elliptic), and includes a light collector 210 and anirradiator 220, which in turn includes a light conductor 222 and aspatial mixer 224. Other geometric shapes may be used for the probe 200and/or for the light collector 210, the light conductor 222, and thespatial mixer 224, as required for the application, includingtriangular, rectangular, hexagonal, octagonal, other multiple facetgeometries, and so forth. Moreover, the principles of the probe 200 maybe used for applications such as surface applications not requiringaccess to the interior of cavities, in which event the overall shape ofsuch probes may be made suitable for the application and need not beelongated.

[0043] Probe output efficiency is maximized by having the irradiationand collection paths essentially separate except for a shared path atthe optical window 240 and through a portion of the irradiator 220. Forexample, the light conductor 222 emits light toward a target 260 fromaround the periphery of the light collector 210, as shown in greatlysimplified form for illustratively a ring source by rays 230. The lightcollector 210 collects light from the target 260 as represented by rays270. Light from the light conductor 222 partially intersects the spatialmixer 224 as it passes through (not shown here; see, e.g., FIG. 5),which mixes the light to remove any reflected images and irradiationartifacts therein. The field of view of the light collector 210preferably is such that any residual reflections and fluorescence fromthe spatial mixer 224 are excluded from collection. While the window 240may be just an opening, an optical element such as a solid flat opticalwindow, a sheet of pliable material, a shaped lens, a conformal windowsuch as a window having a nipple shaped to conform to the Os of thecervix, or a fluid filled sac, or a combination of one or more of suchoptical elements may be used at the position of the window 240 and/orinside of the spatial mixer ahead of the light collector 210 and lightconductor 222 to achieved certain desired mechanical and/or opticaleffects. A conformal window is described in, for example, U.S. Pat. No.5,699,795, issued Dec. 23, 1997 to Richards-Kortum et al. and entitled“Optical Probe for the Detection of Cervical Neoplasia UsingFluorescence Spectroscopy and Apparatus Incorporating Same,” whichhereby is incorporated herein in its entirety by reference thereto.While any such solid window or lens would be shared by the lightcollector 210 and irradiator 220, which preferably are designed to takeinto account any optical effect thereof, the effect of any such solidwindow or lens on optical efficiency is minor compared to efficiencyloses suffered by optical systems that use a beam splitter or a dichroicmirror in the optical path. Moreover, beam splitters and dichroicmirrors tend to generate large amounts of stray light as compared withthe partially common irradiation and collection paths of the probe 200.

[0044] During normal use, the probe 200 is brought into contact with thetarget generally at the optical window 240. The irradiator 220 projectslight along an optical axis of projection coincident with an axis 250which uniformly irradiates a specific surface region of the targetmaterial and penetrates into a volume of the target material through theirradiated surface. The light collector 210 uniformly collects lightfrom this volume along an optical axis of collection coincident with theaxis 250. While the optical axis of projection and the optical axis ofcollection preferably are coincident (e.g. axis 250) to achievesymmetry, this is not a necessary condition provided that theirradiation is sufficiently uniform over the collection volume.

[0045] The light from the irradiator 220 preferably is stable, uniform,and due to interactions with the spatial mixer 224, diffuse (rays of thelight intersecting the target at a multiplicity of angles and from amultiplicity of directions). The diffuse nature of the light improvesits ability to penetrate into the target, including into areas of thetarget which are blocked from receiving normal radiation, with thedistribution of ray angles relative to the axis of light projection fromthe irradiator 220 being selected based on the overall nature of thetarget material. For example, where the target is the human cervix andhigh irradiation efficiency is desired for excitation of weak emissionssuch as fluorescence and Raman, preferably the distribution of rayangles has a maximum near-parallel to the axis of projection, with asmall percentage of the rays being parallel and essentially none of therays being highly deviant from parallel. However, a distribution of rayangles having a maximum at a much greater degree of deviance fromparallel is desirable for some other applications, especiallyapplications in which the surface of the target is moderately toseverely irregular. A distribution of ray angles having a maximumnear-normal to the axis of projection is undesirable, since such lightdoes not penetrate sufficiently into the target. The specificdistribution of ray angles in the light projected from the irradiator220 depends on the material or materials used for and geometry of thespatial mixer 224 as well as the angles of the rays 230 emitted by thelight conductor 222.

[0046] The light collector 210 has a field of view of about the size ofthe optical window 240, a generally uniform collection efficiency overits field of view, and a focal plane in the vicinity of the opticalwindow 240 having a good depth of focus. Preferably, the light collector210 is a telecentric lens system or near-telecentric lens system, whichis particularly suitable because of its uniform collection efficiencyand longer effective depth of focus without appreciable distortion forapplications involving low level responses such as fluorescencespectroscopy of mammalian epithelia, as described in the aforementionedRichards-Kortum patent documents. However, other types of opticalcollectors that have an adequate field of view may be used, if desired,provided that the collected light is compensated for non-uniformityacross the field of view and that any excessive spatial distortion isalso compensated for. Preferably, the light collector 210 is colorcorrected for multi-spectral analysis, and any collection non-uniformityis compensated for by the use of well known normalization algorithms orby well known optical corrections such as the use of a bull's eyefilter. The light collector field of view and depth of focus can vary agreat deal for applications related to cervical and other tissues aswell as non-medical applications.

[0047] Although the distal surface of the light conductor 222 is shownin FIG. 2 to be in the same plane as the distal surface of the lightcollector 210, it may be further extended distally from this plane orrecessed from this plane with adequate means of light transmission tothe target.

[0048] While the probe 200 may be configured and dimensioned as desiredso as to be useful for probing different types of material, organic andinorganic, the optical probe 200 may be configured and dimensioned foruse in diagnosing and/or screening cancerous and pre-cancerous tissuesof mammalian epithelia using fluorescence spectroscopy in the mannerdescribed in the previously cited Richards-Kortum patent documents. FIG.3 shows an optical probe 300 that is based on the generalized probe 200and is configured and dimensioned for probing tissues of the humancervix in the diagnosis of cancers and precancers using tissuefluorescence. In this medical application, the optical probe 300 emits auniform light with a generally normal but somewhat diffuse orientationin the ultraviolet range, the visible range, or both through an opticalwindow 302 which forms the distal end of the probe 300 to excite tissueinto fluorescence within a cylindrical volume, and collects the lowlevel tissue fluorescence through the optical window or probe distal end302 from a cylindrical volume that extends into the tissue substantiallyconcentric with the excited cylindrical volume. In the case of cervicalexamination, the field of view preferably is about 25 mm and the depthof focus is preferably about 8 mm.

[0049] The probe 300 has a housing (shown in cross section) thatincludes a generally cylindrical projecting distal end section 310 and aproximal end section 316 from which fiber optic bundles 330 and 340extend. The distal end section 310 is generally cylindrical andillustratively about 10.8 inches (about 27.4 cm) in length and about aninch (25 mm) in internal diameter at the probe distal end 302. Thedistal end section 310 is slightly flared in a direction away from theprobe distal end 302 to accommodate bulging of the fibers of the bundle340 about the lens system 320; illustratively, the flare is about 2.5degrees beginning at a point about 10.7 cm (4.2 inches) from the window.Preferably, the dimensions of the distal end section 310 allow probeclearance through a speculum or other such devices. The distal endsection 310 and the proximal end section 316 may be constructed as onepiece or separate pieces connected in any desired manner, as by beingthreaded and screwed together, welded, joined with adhesive, clampedtogether, and so forth. The proximal end section 316 is of anyconvenient shape for housing the fiber optics bundles 330 and 340. Whileoptical probes generally may be supported in any convenient manner suchas by a suitable mechanical support, the probe 300 is designed to behand-held and includes a suitable handle 350. Illustratively, the handle350, which has a yoke portion and the proximal end section 316 is of anysuitable shape for receiving the yoke portion, which is rotatablyconnected to the distal end section 316 with screws 430 and 432 (FIG. 4)or any other suitable connector and extends illustratively about 7.5inches from the proximal end section 316. Alternatively, the handle 350may be fixed to the proximal end section 316 or may be part of theproximal end section 316. Any materials suitable for the application maybe used for the probe 300. For example, for cervix examinations, thedistal and proximal end sections 310 and 316 may be made of commonlyavailable stainless steel such as type 304 or equivalent or type 6061T6aluminum that is hard black anodized. The handle 350 may also be made oftype 6061T6 aluminum or other suitable material with or without platingor coating. All aluminum components may also be gold anodized or coatedwith any suitable plating or coating. Many other materials are suitablefor various parts of the probe 300. For example, in medical applicationsthe distal end section 310 which contacts the patient may be made of anyof various medically approved materials, including rigid plastics,pliable plastics, and paper, while other parts such as the handle may bemade of rigid plastic, dense core foam, and so forth. Moreover, thehandle 350 and/or the proximal end section 316 of the probe 300 may becoated with non-slip materials for easier handling, while the distal endsection 310 may be coated with slippery materials to reduce frictionduring insertion.

Irradiator

[0050]FIGS. 3, 4 and 5 show various components of one type of irradiatorfor the optical probe 300. FIG. 3 is a side cutaway view of the opticalprobe 300. FIG. 4 is a cross-sectional view taken normal to the opticalaxis of the optical probe 300 just in front of the distal ends ofnumerous optical fibers of the bundle 340, two of which are referred toby the reference numbers 312 and 314 (FIG. 3). FIG. 5 is across-sectional view taken along the optical axis of the optical probe300 and through part of the distal end section 310. The probe 300terminates in a lens 306 at its distal end 302, although the lens 306may be positioned anywhere in-between the distal end 302 of the probe300 and the distal end of the fibers of the bundle 340 or omittedentirely. The fiber optics bundle 330 from a lens system 320 and thefiber optics bundle 340 pass through the back of the proximal endsection 316 for connection to a light detector 120 (FIG. 1) and a lightengine 110 (FIG. 1) respectively. The fibers of the bundles 330 and 340extend continuously to the light detector 120 and the light engine 110respectively to achieve high efficiency, although the bundles 330 and/or340 may be segmented with intervening connectors located, for example,at or near the back of the proximal end section 316.

[0051] The bundle 340 contains fiber optics for illuminating the target,illustratively twelve hundred fibers, each being approximately 0.2 mm indiameter and having a numerical aperture of, illustratively, 0.28.Suitable fibers are available from a variety of sources, includingCeramoptec Inc. of East Longmeadow, Mass., under the product designationOptran. Illustratively, the fibers of the bundle 340 are separated intotwenty-four groups 401-424 (FIG. 4) of approximately fifty fibers each,the groups 401-424 being routed along the outside surface of the lenssystem 320 from the fiber bundle 340 to evenly-spaced annular positionson a toothed annular form 308 about the distal end of the lens system320 to form a ring light source. During manufacture, the fibers of thebundle 340 are held in place about the casing for the lens system 320using various tooling and then potted in a manner well known in the artusing preferably non-fluorescent potting material. The gathering of thefibers near the proximal end of the lens system 320 causes a bulge onone side of the probe 300 that is accommodated by the flaring of thedistal end section 310. Note that the irradiation fibers 310 may bebundled for connection to the light engine in other ways. For example,the fibers may be gathered into two or more separate bundles rather thaninto the single larger diameter bundle 340, which would reduce theamount of bending of the individual fibers and result in less bulging.As a further example, the fibers may also be arranged coaxially aboutthe fiber bundle 330. Note also that the use of twenty-four groups401-424 is illustratively, and more or fewer groups containing more orfewer fibers may be used as desired. The fibers need not be grouped, butmay be continuously arranged about the inside of the body 304, ifdesired. The fibers may be randomized to provide some mixing of anyspatial definition from the light engine. Note that the fibers of thebundle 340 may be held in place on the casing of the lens system 320 byother techniques, such as by other suitable adhesives and evenmechanical retainers before being ground and polished on the ends.Alternatively, the fibers of the bundle 340 may be mounted on the insidesurface of the distal end section 310 (not shown), or may be mounted ona form (not shown) that is disposed between the distal end section 310and the lens system 320. The outside generally cylindrical surfaceformed by the potted fibers from the bundle 340 on the lens system 320is wrapped with Teflon® tape to facilitate probe assembly, although avariety of other coatings and covering materials may be suitable aswell.

[0052] The form 308 on the distal end of the lens system 320 serves toangle the distal ends of the fibers of the bundle 340 at about tendegrees toward the optical axis of the lens system 320. Duringmanufacture, the angled fibers are sliced normal to the optical axis ofthe lens system 320 and ground and polished in a well-known manner toachieve surfaces that are themselves angled about ten degrees relativeto the respective axes of the fibers of the bundle 340. Any suitableanti-reflective coating may be applied to the ends of the fibers toincrease transmission efficiency. As a result of this geometry, thecenter of the light cone emitted from the end of each fiber of thebundle 340 is angled about fifteen degrees toward the optical axis ofthe lens system 320.

[0053] The optical probe 300 also includes a spatial mixer, which isimplemented by providing a particular finish to or applying a particularmaterial to the inside wall 304 of the distal end section 310.Generally, the surface 304 forming the spatial mixer is a substantiallynon-fluorescing material having or having been finished to have highdiffuse reflectivity in preferably the ultraviolet and visiblewavelengths and to strongly forward-scatter the wavelengths of lightexiting the distal ends of the fibers of the bundle 340. For example,where the distal end section 310 is a stainless steel tube, the spatialmixer surface 304 is achieved by grinding and honing the inside of thetube to achieve a suitable surface finish, illustrative an 8 to 16microinch (0.2 to 0.4 micrometer) finish, and then electropolishing orchemically polishing the finish to improve uniformity and efficiency andto reduce backscatter. Alternatively, the spatial mixer 304 may bealuminum, metal, mylar, or other type of foil that has suitable surfaceproperties and is made to line the inside of the distal end section 310.The specific property for the spatial mixer surface 304 is determined bybalancing reflection efficiency on the one hand and uniformity anddiffusivity on the other hand. Hence, even near-specular finishes on theorder of 4 microinches (0.1 micrometer) may be suitable in somearrangements, although care should be taken when using near-specularfinishes not to re-image the output of the fibers 310 at the target fromthe spatial mixer surface 304. In other arrangements, a surface finishgreater than 16 microinches (0.4 micrometers) may be suitable wheregreater uniformity is required and efficiency is less of a concern.

[0054] Most of the light from the distal ends of the fibers of thebundle 340 is directed toward the probe distal end 302, but the lightspreads with a half angle of about sixteen degrees so that some lightinitially encounters the spatial mixer surface 304 and isforward-scattered to augment light intensity generally in the peripheryof the field of view of the lens system 320 and to add an additionalprofusion of ray angles to the light at the probe distal end 302,thereby causing a uniform diffuse light to occur in the vicinity of theprobe distal end 302. Hence, some number of reflections of light rayswithin the spatial mixer 304 is desirable. However, reflecting too muchof the light too many times would result in reduced irradiationefficiency because multiply reflected light would suffer attenuation inthe spatial mixer 304. Such multiply reflected light is undesirableunless adequate power is available from the light engine 110. Anexcessive number of reflections would result in an increasing number ofrays being nearly parallel to the general orientation of the targetsurface in the vicinity of the probe distal end 302. Such rays wouldfail to penetrate sufficiently deeply into the target (e.g., tissue) toexcite fluorescence throughout the desired volume of material.

[0055] A lens 306 is positioned at the distal end 302 to serve as theoptical window of the probe 300. The lens 306 is provided with anysuitable surface contour and is made of any suitable material orcombination of materials having good optical properties and lowfluorescence, such as ground glass, quartz, fused silica, or moldedacrylic such as type EXP-X72 available from CYRO Industries, Inc. ofRockaway, N.J., which is a non-additive version of the company's typeS-10 Acrylite® acrylic molding compound. The lens 306 may have anydesired antireflective (“A/R”) coating on either surface or on bothsurfaces, and any other characteristics as required by the lens system320. The lens 306 is sealed to the inside wall of the distal end section310 to protect the fibers of the bundle 340, the lens system 320, andother internal components of the probe 300 from contamination and damageduring use.

[0056] When placed at the distal end 302 of the probe 300 as shown, thelens 306 is able to contact and compress the target. However, the lens306 may be spaced away from the distal end 302 of the probe 300, eithernear the distal end of the lens system 320 and the ends of the fibers ofthe bundle 340 (see, e.g., FIG. 7), or positioned anywhere between thedistal end 302 of the probe 300 and the distal end of the lens system320. Positioning a lens near the distal end of the fibers of the bundle340 and spaced away from the ends of the fibers of the bundle 340 by anysuitable distance, e.g. less than about 8 mm and preferably about 1 mm,places any reflected image of the distal end of the fibers of the bundle340 outside of the field of view of the lens system 320, therebyavoiding any adverse impact such a reflected image may have on the lightsought to be collected. For example, a reflected image from a lightsource seriously impacts the detection of a reflection image of thetarget since the wavelength or wavelengths of both reflections would bethe same. However, a reflected image from a lens has less impact on thedetection of a fluorescence or Raman emission, since the wavelength orwavelengths of a fluorescence or Raman emission differ from that of thereflected image and are typically isolated by bandpass filters or aspectrograph. Positioning a lens further from the distal end of thefibers of the bundle 340 requires the use of a very good anti-reflectivecoating on the lens or the use of other appropriate techniques to avoidgenerating a reflected image of the distal end of the fibers of thebundle 340.

[0057]FIG. 5 is a longitudinal cross-section through the spatial mixer304 of the optical probe 300 (lens 306 omitted for clarity), and showsthe behavior of various exemplary rays of light therein. The spatialmixer 304 is illustratively about 65 mm in length and about 25 mm indiameter. The angled distal ends of the fibers of the bundle 340 biaslight toward the center of the field of view of the lens system 320, asrepresented by ray 514 which emanates from an illustrative fiber 510,and by ray 524 which emanates from an illustrative fiber 520. Lightspreads out in a roughly symmetrical conical pattern from each fiber ina well understood manner, as from the ends of the illustrative fibers510 and 520 as represented by rays 512 and 516 and rays 522 and 526respectively. The spatial mixer 304 functions by redistributing aportion of the solid angle emitted by each of the fibers of the bundle340, as represented by the forward scattered components of rays 512,516, 522 and 526, resulting in spatial mixing onto the target at or nearthe probe distal end 302. This redistribution as well as the angleddirect light represented by rays 514 and 524 achieve a multiplicity ofray angles in the vicinity of the probe distal end 302. Most of the raysare near-parallel to the optical axis 530 of the light detector (notshown) with some rays at the edge of the probe distal end 302 beingparallel to the optical axis 530, so that light efficiently penetratesinto the target (e.g., tissue).

[0058] The various components and materials used in the irradiationsystem of the optical probe 300 are selected to be capable of handlingthe irradiation power desired. For example, one use of the optical probe300 for examination of the human cervix involves power out of the probedistal end 302 to range from about 20 to 50 mW at 337 nm, 380 nm, and460 nm. Systems with power on the order of about 100 mW or greater maybe used if desired to reduce total integration times. Illustratively,the spatially mixed light from the probe 300 penetrates up to about 300microns into the cervical tissue, depending on wavelength, to excitefluorescence therein. The optical probe 300 may also be used forapplying light treatment to tissue, which can involve higher powerlevels up to the tolerance level of the tissue. However, non-tissueapplications may involve even higher power levels, so that thecomponents and materials of the irradiation system used in suchapplications should be selected accordingly.

Light Collector

[0059]FIG. 6 is a plan side cutaway view of the optical probe 300 ofFIG. 3 showing various components of the lens system 320 having theplano-convex lens 306 at the probe distal end 302. The use of lens 306in conjunction with the lens system 320 forms a true telecentric lenssystem, the lenses of which illustratively are as follows. Lens 306 is aplano-convex silica lens having a diameter of 25.4 mm, a thickness of4.0 mm (lens thickness being measured along its optical axis), a distalsurface radius of infinity, and a proximal surface radius of 91.69 mm.Lens 606 is a cemented doublet acromat with a convex-convex element ofBAF10 glass having a diameter of 19.0 mm, a thickness of 11.4 mm, adistal surface radius of 24.47 mm, and a proximal surface radius of16.49 mm, and a concave-convex element of FD10 glass having a diameterof 19.0 mm, a thickness of 3.0 mm, a distal surface radius of 16.49 mm,and a proximal surface radius of 131.65 mm. Lens 610 is a cementednegative doublet acromat with a concave-concave element of BK7 glasshaving a diameter of 12.5 mm, a thickness of 2.0 mm, a distal surfaceradius of 30.83 mm, and a proximal surface radius of 23.47 mm, and aconcave-convex element of SF5 glass having a diameter of 12.5 mm, athickness of 1.6 mm, a distal surface radius of 23.47 mm, and a proximalsurface radius of 69.20 mm. Lens 614 is a cemented doublet acromat witha convex-convex element of BAF11 glass having a diameter of 15.0 mm, athickness of 6.3 mm, a distal surface radius of 17.97 mm, and a proximalsurface radius of 11.20 mm, and a concave-convex element of SF10 glasshaving a diameter of 15.0 mm, a thickness of 1.8 mm, a distal surfaceradius of 11.20 mm, and a proximal surface radius of 85.31 mm. Lens 618is a cemented doublet acromat identical to lens 614. Suitable spacers608, 612 and 616 and other structures such as flange 602 are used tokeep the lenses 606, 610, 614 and 618 in place and properly spacedapart, and a resilient O-ring 604 is used against lens 606 to seal thechamber containing the lenses 606, 610, 614 and 618. Illustratively, thespacing between lenses 306 and 606 is 142.50 mm, between lenses 606 and610 is 11.03 mm, between lenses 610 and 614 is 3.34 mm, between lenses614 and 618 is 1.00 mm, and between lens 618 and an image plane 620 atthe end surface of the fiber bundle 330 is 3.00 mm. The lens 306 andlens system 320 is focused at a object point about 1 mm beyond thedistal end of the probe 300 and into the target, and is designed tofocus the target image onto the image plane at the end of the fiberbundle so as to avoid loss of power density while reducing the imagesize. The ratio of the field of view of the optical probe 300 to theimage size on the image plane 620 is approximately 6X, withapproximately f/2 on the image plane at the fiber optic cable 330 toallow adequate depth of focus in the vicinity of the probe distal end302.

[0060] Stray light is blocked from the image plane 620 at the endsurface of the fiber bundle 330 by restricting the field of view of theoptical probe 300 using an aperture such as 621 and by incorporating oneor more additional apertures as desired. Stray light originates in manyways, including reflections off of distal window or lens surfaces andbackscatter from the spatial mixer surface 304. The field limitingaperture in the system 320 is the aperture 621 over the image plane 620at the end surface of the fiber bundle 330. Illustratively, aperture 621is 3.9 mm in diameter and the fiber bundle 330 is 4.0 mm square. Anotheraperture in front of the lens 610 also is effective in blocking otherstray light from areas outside of the primary field of view.

[0061] A modification of the probe 300 and lens system 320 is shown inFIG. 7. The lens 306 at the distal end 302 of the probe is absent.Instead, a lens 706 is provided, which is recessed from the probe distalend 302 and mounted well within the spatial mixer 304 adjacent the lenssystem 720 and spaced 1 mm from the distal ends of the fibers of thebundle 340. An additional lens or window 707 is placed at the distal endof the lens system 720 to seal the entire lens system 720 and preventdust from depositing on the optics or the optically black sidewall ofthe casing of the lens system 720. In applications involving pliabletargets such as, for example, the human cervix, the probe 700 with anopening at the probe distal end 302 tends to stabilize more securely onthe cervix when cervical tissue protrudes into the distal end segment310. In this modification, the lens system 720 in conjunction with thelenses 706 and 707 do not form a telecentric lens system, but do achievesufficiently uniform light collection to avoid the need for extensiveoptical correction. The lenses of the probe 700 illustratively are asfollows. Lens 706 is preferably a concave-convex (meniscus) acrylic lenshaving a diameter of 25.0 mm, a thickness of 2.0 mm (lens thicknessbeing measured along its optical axis), a distal surface radius of 82.97mm, and a proximal surface radius of 76.20 mm. However, the lens 706 mayinstead be a flat acrylic window, if desired, which would occasion onlya minor performance reduction. The protective window 707 is a flatsilica cylinder having a diameter of 20.0 mm and a thickness of 3.0 mm.The other lenses and spacers of the lens system 720 are the same as thelenses and spacers of the lens system 320, except that the spacingbetween the object and lens 706 is 59 mm, between lens 706 and theprotective window 707 is 1 mm, and between the protective window 707 andlens 606 is 80 mm. The lens system 720 is focused at a point about 2 mminside of the distal end of the probe 700. This focal plane will usuallybe on cervical tissue for applications in which the target is the humancervix. Cervical tissue will likely protrude into the distal end segment310 as a result of the natural shape of the cervix or light pressureapplied to hold the probe 700 in place during use. The lens system 720is also designed to focus the target image onto the image plane 620. Theratio of the field of view of the optical probe 700 to the image size onthe image plane 620 is approximately 6X, with approximately f/2 at theimage plane into the fiber optic cable to allow adequate depth of focusin the vicinity of the probe distal end 302.

[0062] Stray light is blocked from the image plane 620 at the endsurface of the fiber bundle 330 by two principal apertures. One of theprincipal apertures in the lens system 720 is the aperture over thedistal surface of the lens 610, which illustratively has a diameter of6.4 mm and is spaced 1.00 mm from the distal surface of the lens 610.The other principal aperture in the lens system 720 is a field limitingaperture 721 over the image plane 620 at the end surface of the fiberbundle 330, which illustratively has a diameter of 3.9 mm and is spaced2.00 mm from the image plane 620. Both apertures are active incontrolling stray light, and since the lens system 820 is nottelecentric, the aperture over the distal surface of the lens 610defines the f-number or numerical aperture of the light collector.

[0063] The principal apertures in the lens systems 320 and 720 includean angled inside annular surface, which redirects stray light away fromthe image plane 620. FIG. 8 shows how various illustrative rays that arereflected from a lens such as lens 706 of the optical probe 700 (FIG. 7)near the distal end 302 of the probe 700 either are blocked from theimage plane 620 or redirected by the aperture 721. The inside annularsurface of the aperture 721 is angled preferably 45° relative to theoptical axis of the probe 700. Stray light coming through the lenssystem 720 from lens 706 and window 707 and from other sources andprojecting just outside of the aperture either is reflected once anddirected harmlessly through at least two lenses onto apertures and/orthe inside optically black wall of the casing for the lens system 720,see, e.g., ray 804; or is reflected twice by two diametrically opposed45° angled surfaces and exits the lens system 720 altogether, see, e.g.,rays 806 and 808.

Combining the Light Collector and Irradiator

[0064] Preferably, care is taken to ensure good alignment of the opticalaxis of the light collector 210 (FIG. 2) with the axis of the spatialmixer 224 to avoid backscattered light from the spatial mixer 224 fromentering into the field of view of the light collector 210. Generally,the field of view of the light collector 210 is narrow enough to excludethe inside wall of the spatial mixer 224 when alignment is proper, butotherwise is as wide as possible to permit viewing of an area of thetarget very slightly less than the overall diameter of the probe 200.Any misalignment would therefore allow reflected and backscattered lightinto the field of view of the probe 200 as a crescent of light.

[0065] Proper alignment of the optical axis of the light collector 210with the axis of the spatial mixer 224 may be established and maintainedin any suitable manner. For example, the distal probe section 310 andthe proximal probe section 316 the probes 300 and 700 may be made of asingle piece with the lens system 320 being rigidly retained therein.Alternatively, the distal probe section 310 and the proximal probesection 316 may be made of separate pieces, with the lens system 320being rigidly retained therein by, for example, suitable structuralmembers of the proximal probe section 316, and the distal probe section310 being threaded and screwed into a prealigned threaded opening in thestructural members of the proximal probe section 316.

[0066] Preferably, care is taken to ensure that the proper focaldistance is maintained between the light collector 210 and the window240. This focal distance is predetermined by optical design, and theproper focal distance is established by proper manufacture to toleranceand proper assembly and alignment of components. Alternatively, thefocal distance may be mechanically variable, as in the case where thedistal probe section 310 is threaded and screwed into a threaded openingin the proximal probe section 316, adjusted as needed, and fixed withany suitable device such as a set screw or various reference mechanicalstops. The use of various stops enables repeating a setting.Alternatively, the focal length may be optically variable byincorporating a small motor, screw and guides into the light collector210 to electrically remotely reposition the lens as required to achieveproper focus. These and other techniques for achieving proper focus arewell known in the art and may be used as desired in connection with thegeneralized optical probe 200.

[0067] The axial placement of the distal end of the light collector 210(FIG. 2) relative to the ring-like distal end of the light conductor 222of the generalized probe 200 may be varied to achieve any desired designobjective, provided that the uniform and diffuse nature of the lightemitted at the window 240 is not adversely affected, and provided thatany stray light going to the light collector 210 is controlled. Forexample, the distal end of the light conductor 222 may be placedgenerally in the plane of the distal end of the light collector 210, asin the case of the optical probe 300, behind the plane, or in front ofthe plane. Similarly, lens that optically participate with the lightcollector 210 in the collection of light may be located anywhere betweenthe plane of the distal end of the light conductor 222 and the window240, provided that the uniform and diffuse nature of the light emittedat the window 240 is not adversely affected. A lens such as lenses 306and 706 used for mechanical protection and contamination control mayalso be located anywhere between the plane of the distal end of thelight conductor 222 and the window 240, provided that any stray lightfrom reflectance is controlled.

[0068] A lens placed in front of the distal end of the light conductor222 generates stray light by reflecting a portion of the light from thelight conductor 222. When the lens is located near both the distal endof the light conductor 222 and the distal end of the light collector210, the light reflected by the lens tends to be outside of the field ofview of the light collector 210. However, when the lens is located adistance from both the distal end of the light conductor 222 and thedistal end of the light collector 210, a substantial amount of the lightreflected by the lens tends to be inside of the field of view of thelight collector 210 and is seen as disc-like artifacts. Varioustechniques are useful for reducing the effect of such reflections. Forexample, anti-reflection (“A/R”) coatings may be used to reduce theamount of reflected light. Where the light being collected is of adifferent wavelength than the irradiation light, blocking filters mayalso be used to reduce the amount of reflected light detected.

[0069] A useful and particularly efficient approach for connecting thelight conductor 222 and the light collector 210 to respectively a lightengine (e.g., light engine 110 of FIG. 1) and a light detector (e.g.,light detector 120 of FIG. 1) is continuous optical fibers from thelight engine to the light conductor 222. However, due to the cost ofthis approach, other approaches may be better suited to certainapplications. Alternative approaches include providing opticalconnectors on the probe, to which separate cables from the light engineconnect. These separate cables may be made of optical fibers or otherlight conductors. For example, liquid light guides may be used for theirradiation light. Liquid light guides are flexible and have a costadvantage over optical fiber optics, but also tend to have a variableoutput which may need to be compensated for at the light detector. Anillustrative compensation technique entails installing an edge-of-fieldlight sensor component in the probe to monitor light output at theprobe. Based on conditions of uniform light irradiation, a baseline ofthe liquid light guide is established. Then, the light output at theprobe is monitored with the edge-of-field sensor components inconjunction with the light detector prior to each use to establish acalibration factor for each patient setup and to detect and correct forchanges during each patient analysis. Continuous multipoint monitoringmay be needed if there is spatial content to the transmission variationscaused by movement of the cable.

Light Irradiation and Collection in Optical Probes Having DisposableComponents

[0070] For applications in which avoidance of contamination isimportant, an optical probe may be designed as a one piece unit that isfully reusable after cleaning and decontamination, or as a two pieceunit having one section with delicate and/or expensive components thatis reusable without cleaning or decontamination and a protective durablesection that is reusable with cleaning and decontamination, or as havinga fully reusable section and a protective disposable section that isdiscarded after several or preferably one use and replaced with anidentical but new and clean disposable. FIG. 9 shows an optical probethat has a fully reusable section 900 and a disposable section 910. Asuitable connector component 920 on the reusable section 900 engages asuitable connector component 912 on the disposable 910 to hold thedisposable 910 in place in proper alignment with the reusable section900. A variety of connection mechanisms are suitable, including threadedfixtures, bayonet style fixtures, spring loaded clamps, friction fitfixtures, and so forth.

[0071]FIG. 10 shows an example of the fully reusable optical probesection 900 suitable for use work with a disposable optical probesection such as shown in FIGS. 24-30. The probe 900 has a housing (shownin cross section) that includes a generally cylindrical projectingdistal end section 1010 and a proximal end section 1016 to which ahandle 950 is rotatably connected and from which fiber optic bundles 330and 940 extend. The distal end section 1010 is generally cylindrical andillustratively about 18.5 cm in length and about 25 mm in diameter atthe distal end 1002, the overall length of both sections 1010 and 1016being about 28.5 cm. The distal end section 1010 and the proximal endsection 1016 may be constructed as one piece or separate piecesconnected in any desired manner, as by being threaded and screwedtogether, welded, joined with adhesive, clamped together, and so forth.The proximal end section 1016 is of any convenient shape for housing thefiber optics bundles 330 and 940 and to receive the handle 950, whichextends illustratively about 19 cm from the proximal end section 1016.As the reusable probe section 900 does not contact the target, a widevariety of materials may be used for it, including all of the materialssuitable for the probe 300 as well as materials that may not be suitablefor the probe 300 because of, for example, patient contact restrictionsin the case of medical applications.

[0072] The reusable probe section 900 includes a light collector,illustratively the lens system 720, and part of an irradiator,illustratively a light guide 1020. The spatial mixer preferably isincluded in the disposable. Although a light conductor made of fiberssuch as the fibers 340 in the probe 300 may be used instead of the lightguide 1020, the light guide 1020 is made with preferably a generallycylindrical shape which does not require that the distal end section1010 of the reusable probe section 900 be flared, thereby simplifyingthe manufacture of the disposables of FIGS. 20-23 that mount on thereusable probe section 900. The light guide 1020 is suitable for use inthe optical probe 300 as well. Preferably, the fiber bundle 330 isrouted straight from the lens system 720 through the back of theproximal section 1016, and the light guide 1020 is provided with anopening through which the fiber bundle 330 passes. Alternatively, thelight guide may be made to be symmetrical (not shown) while an assemblyof mirrors, prisms, and the like may be used to route the image from theend of the lens system 320 through a notch in such a light guide andonto the image plane of an optical fiber bundle or connector (not shown)that is not coaxial with the lens section 720.

[0073] It will be appreciated that both the lens system 720 and thelight guide 1020 in the reusable probe section 900 are illustrative, andthat other lens systems, light guides, fiber arrangements, andcombinations of lens, fibers, light guides, and so forth may be usedinstead. For example, FIG. 11 shows a reusable probe section 1100 inwhich the distal end 1002 is open and a lens or window 1122 is recessedinto a lens system 1120, which is otherwise similar to the lens system720.

[0074] The light guide 1020 may be manufactured by various techniques.For example, the light guide 1020 is made of fused silica, and may bemanufactured in two pieces, including a short free-form light pipecoupled to a concentric cylindrical light pipe as shown in FIGS. 12-19,or in a single piece, such as a long free-form light pipe (not shown).Cladding, a vacuum deposited film, or another suitable material on theinside and outside surfaces of the fused silica is used to achieveinternal light reflection, and the light pipe itself may be hollow orliquid filled instead of solid fused silica. These implementations mayinclude means known in the art for improving light uniformity, includingthe use of a square clad rod light integrator or other such means ofdiffusing image artifacts at the input. Light is emitted from the lightguide 1020 in a generally annularly continuous manner rather than as aring of merging cones as from the ends of the fibers of the bundle 340in the probe 300.

[0075]FIG. 12 shows a cross section along the axis of a cylindrical part1200 of a two piece light guide, which is coupled to either free formsection 1400 or free form section 1700 to complete the light guide.Section 1200 is a cylindrical light guide having a fused silica core1204 contained within aluminum tubes 1202 and 1206. Illustratively, thecylindrical section 1200 is 129.5 mm (5.10 inches) long. The core 1204has an inside diameter of 20.0 mm (0.787 inches) and an outside diameterof 24.0 mm (0.945 inches), and is fabricated using techniques well knownin the art. The core 1204 is suitably clad to achieve a numericalaperture of preferably from about 0.25 to 0.4, and is then covered withan opaque coating to control stray light. Suitable cladding materialsand opaque materials are available from various sources, includingChemat Technology Inc. of North Ridge, Calif., and Optical PolymerResearch, Inc. of Gainesville, Fla. Aluminum tube 1206 has an insidediameter of 19.0 mm (0.748 inches) and an outside diameter of 19.9 mm(0.783 inches), while aluminum tube 1202 has an inside diameter of 24.1mm (0.949 inches) and an outside diameter of 25.0 mm (0.984 inches). Thealuminum tubes 1202 and 1206 preferably are black anodized, and areinstalled after cladding and coating is completed but before the ends ofthe fused silica core 1204 are ground and polished. A view of theproximal end of the section 1200 is shown in FIG. 13.

[0076]FIG. 15 shows a cross section along the axis of a free-form fusedsilica light guide section 1400 made using fabrication techniques wellknown in the art. Illustratively, the free form section 1400 is 45.7 mm(1.8 inches) long, and includes a suitably clad fused silica core 1404which is placed within an aluminum tube 1402 before grinding, polishingand A/R coating of the ends thereof. After cladding is applied, the core1404 is potted inside of the aluminum tube 1402, using any suitablepreferably non-fluorescent potting material. The core 1404 at the distalend of the section 1500 has an inside (diameter of 20.0 mm (0.787inches) and an outside diameter of 24.0 mm (0.945 inches), and at theproximal end has a diameter of 8.0 mm (0.315 inches) to mate up with aliquid light guide or fiber optic cable. A channel, which is referred toby the numeral 1408, is provided in the free form section 1400 for thepassage of the fiber bundle 330 (FIG. 10). Illustratively, channel 1408measures 15.2 mm (0.60 inches) wide and 27.9 mm (1.10 inches) long, andis spaced from the proximal end of the section 2000 by 27.9 mm (1.10inches). A view of the distal end of the section 1400 is shown in FIG.14, and a view of the proximal end of the section 1400 is shown in FIG.16. The sections 1200 and 1400 are coupled using any suitable techniquesuch as a index matching optical fluids, and suitable A/R coatings.

[0077]FIG. 18 shows a cross section along the axis of a free-formsection 1700 made of a large number of cladded fused silica fibers usingfabrication techniques well known in the art. Illustratively, about 24cladded fibers are fused together to form the free form section 1700,the dimensions of which are the same as the free form section 1400. Thesection 1700 is potted inside of an aluminum tube 1702. A view of thedistal end of the section 1700 is shown in FIG. 17, and a view of theproximal end of the section 1700 is shown in FIG. 19. The sections 1200and 1700 are coupled using any suitable technique such as a indexmatching optical fluids, and suitable A/R coatings.

[0078] As can be seen from FIGS. 14-19, the use of openings in the freeform sections 1400 and 1700 as well as the asymmetrical design thereofdoes not permit light to be uniformly annularly distributed therein.However, the annular uniformity of the light is improved by thecylindrical section 1200. Other measures to improve the annularuniformity of the light include varying the light guide wall thicknessat the entrance transition or providing deflectors to deflect the lightaround the opening and then rotating and counter rotating the lightaround the fused silica core 1204. Using a square spatial mixer at theinput may also be desirable for improving the annular uniformity of thelight.

[0079] While the light guide 1020 emits light in a generally annularlycontinuous manner using techniques such as those described withreference to FIGS. 14-16 and 17-19, other techniques use multiple lightguides to emit light from discrete light emitting areas in the natureof, for example, a ring of merging cones, essentially like the cones oflight that are emitted from the ends of the optical fibers of the bundle340 in the probe 300. FIG. 20 shows another type of optical probe 1800that is based on the generalized probe 200 and is configured anddimensioned for probing tissues of the human cervix in the diagnosis ofcancers and precancers using tissue fluorescence. In this medicalapplication, the optical probe 1800 emits a uniform light with agenerally normal but somewhat diffuse orientation in the ultravioletrange, the visible range, or both through an optical window 1802 whichforms the distal end of the probe 1800 to excite tissue intofluorescence within a generally cylindrical volume, and collects the lowlevel tissue fluorescence through the optical window or probe distal end1802 from a generally cylindrical volume that extends into the tissuesubstantially concentric with the excited cylindrical volume. In thecase of cervical examination, the field of view preferably is about 25mm and the depth of focus is preferably about 8 mm.

[0080] The probe 1800 includes a generally cylindrical distal section1810 and a proximal section 1840 from which a flexible conduit 1858extends. The distal section 1810 illustratively projects 4 inches (10cm) and is an inch (25.4 mm) in internal diameter at the optical window1802 at the probe distal end. Preferably, the dimensions of the distalsection 1810 allow clearance through a speculum or other such device.The proximal section 1840 is of any convenient shape for enclosing, forexample, a number of individual light guides, liquid light guides 1842and 1844 being representative, a light collector such as the lens system1848, a light detector such as a CCD camera 1850, a filter wheel 1852containing a number of different filters (not shown), and a suitableactuator such as a stepper motor 1854 for rotating the filter wheel1852. The light guides in the probe 1800 are arranged so as to emitlight toward a target in the proximity of the optical window 1802 fromaround the periphery of the lens system 1848. The overall length of bothsections 1810 and 1840 illustratively is 12 inches (30.5 cm). Thespatial mixer preferably is contained in the distal section 1810. Whileoptical probes may be handheld or otherwise supported in any convenientmanner, the probe 1800 is designed to be supported by a support arm (notshown) which attaches to the housing 1846 or other structural member ofthe proximal section 1840 in any suitable manner. Preferably, the liquidlight guides such as 1842 and 1844 of the probe 1800 extend continuouslyto the light engine 110 through a flexible conduit 1858 affixed to thehousing 1846 to achieve an efficient transmission of light to the probe1800 from the proximal ends of the liquid light guides into which lightis coupled at the light engine 110. However, the liquid light guides maybe segmented if desired with an intervening connector located, forexample, on the proximal section 1840. Moreover, the light transmissionmedium from the light engine 110 to the probe 1800 may be a differenttype of light guide than the type of light guide used in the probe1800—for example, the light guides in the probe 1800 may be of the fusedsilica type while a liquid light guide or guides may be used between theprobe 1800 and the light engine 110—or may be an entirely different typeof light transmission medium such as, for example, a conduit containingmirrors for directing light. Alternatively, the light guides in theprobe 1800 may be routed to a light emitting diode (“LED”) or array ofLEDs (not shown) mounted in the housing 1846, in which case electricalcables for the LEDs rather than a light transmission medium is routedthrough the conduit 1858. An electrical power and signal cable 1856 fromthe CCD camera 1850 is routed to the system controller and processor 100through the flexible conduit 1858. Any materials suitable for theapplication may be used for the probe 1800.

[0081] The distal section 1810 and the proximal section 1840 may beconstructed as one piece or as separate pieces connected in any desiredmanner. FIG. 20 shows a two piece construction wherein the distalsection 1810 is a disposable 1820 (shown in cross section), the proximalsection 1840 is a fully reusable section having a housing 1846 (shown incross section), and the disposable 1820 is connected to the housing 1846or other structural member of the proximal section 1840 using anysuitable connection technology (generally indicated at 1830) to hold thedisposable 1820 securely in place in proper alignment with the proximalsection 1840 during an examination, but to allow for easy release of thedisposable 1820 after the examination is completed. A variety ofconnection mechanisms are suitable, including threaded fixtures, bayonetstyle fixtures, spring loaded clamps, friction fit fixtures, latches,tab and slot features, and so forth. In the embodiment of FIG. 20, thedistal projection of the reusable proximal section 1840 of the probe1800 is not flared, thereby simplifying the manufacture of disposablesthat mount on the reusable probe proximal section 1840. Suitabledisposables include those shown in FIGS. 24-30.

[0082] The lens system 1848 forms an image on the CCD array of the CCDcamera 1850. The image is represented as digital data and communicatedto a system controller and processor 100 over the electrical cable 1856.The liquid light guides 1842 and 1844 are sufficiently flexible to berouted around the lens system 1848, the filter wheel 1852, and thestepper motor 1854, and are sufficiently flexible along their coursethrough the conduit 1858 to avoid unduly interfering with positioning ofthe probe 1800 in connection with an examination. Illustratively, aliquid light guide having a 1.5 inch (3.8 cm) radius maximum bendspecification is satisfactory. It will be appreciated that both the lenssystem 1848, the CCD camera 1850, the filter wheel 1852, and the steppermotor 1854 are illustrative, and that other lens systems, other types ofcameras, other type of filter arrangements, and combinations thereof maybe used instead.

[0083] The disposable 1820 includes a tubular member 1822 having asuitable interior surface to achieve spatial mixing, an optical element1824 such as an optically transparent plate or lens which is recessedfrom the optical window 1802, and a suitable attachment mechanism at theconnector site 1830. Illustrative disposables having spatial mixersparticularly suitable for use with the arrangement of light guides inthe probe 1800 are described in further detail with reference to FIGS.28-30.

[0084]FIGS. 21 and 22 show an illustrative technique for introducinglight from the light engine 110 into the light guides of the probe 1800.Illustratively, the probe 1800 has seven light guides 1911, 1912, 1913,1914, 1915, 1916 and 1917. While a variety of different types of lightguides may be used, illustrative the light guides 1911, 1912, 1913,1914, 1915, 1916 and 1917 are liquid light guides made of a hollowtubular sheath of, for example, a Teflon® FEP fluoropolymer filled witha suitable saline liquid and plugged at both ends with a one inch (2.54cm) long slug of fused silica having a plano-plano lens and finishedwith a suitable anti-reflective coating. Suitable liquid light guidesare well known in the art and are available from a variety of sources,including Translight Inc. of Pleasanton, Calif., under the productdesignation UV LLG, 3 mm by 6 foot. Illustratively, each of the liquidlight guides 1911, 1912, 1913, 1914, 1915, 1916 and 1917 has an insidediameter of 0.120 inches (3 mm), an outside diameter of 0.16 inches (4mm), and a total length of six feet. The proximal ends of the liquidlight guides 1911, 1912, 1913, 1914, 1915, 1916 and 1917 preferably arepacked as densely as is feasible by stripping one-half inch (1.27 cm) ofthe sheathing from each of the fused silica slugs and clustering theslugs as shown in FIG. 22, where they are retained within an orifice ina plate 1904. Light from the light engine 110 is focussed onto the endsof the slugs retained in the plate 1904 and is thereby coupled into theliquid light guides 1911, 1912, 1913, 1914, 1915, 1916 and 1917.

[0085]FIG. 21 is a cross section through an illustrative mountingassembly 1900, in which three of the liquid light guides 1917, 1911 and1914 are visible. The slugs at the end of the outside liquid lightguides 1917 and 1914 are slightly slanted, illustratively 5 degrees,toward the centrally positioned slug at the end of the liquid lightguide 1911. The liquid light guides 1911, 1912, 1913, 1914, 1915, 1916and 1917 are held in proper alignment by holes formed in a plate 1906,which is held in a spaced-apart relationship from the plate 1904 bysidewalls 1902 and 1908. The sidewalls 1902 and 1908 include flanges(not shown) by which the mounting assembly 1900 is attached to the lightengine 110, thereby forming an enclosed chamber in which light from thelight engine 110 is focused onto the proximal ends of the liquid lightguides 1911, 1912, 1913, 1914, 1915, 1916 and 1917.

[0086]FIG. 23 shows one possible technique for retaining the distalsections of the liquid light guides 1911, 1912, 1913, 1914, 1915, 1916and 1917 in the reusable section 1840 of the optical probe 1800,although many other retaining techniques well known in the art may beused as well. The distal sections are evenly arranged in a circle aroundthe lens system 1848, the circular arrangement being coaxial with thelens system 1848 with a radius of 0.4 inches (1 cm) as measured to theaxis of the liquid light guides. The lens system 1848 rests within acylindrical form 1930, which has seven slots for receiving respectivelythe distal segments of the liquid light guides 1911, 1912, 1913, 1914,1915, 1916 and 1917. Illustratively, 2 inches (5 cm) of the liquid lightguides 1911, 1912, 1913, 1914, 1915, 1916 and 1917 lie in these slots. Aprotective sheathing 1920 of any suitable material such as stainlesssteel having an thickness of 0.02 inches (0.5 mm), for example, encasesthe distal segments of the liquid light guides 1911, 1912, 1913, 1914,1915, 1916 and 1917 in the form 1930 to protect them from mechanicalshock and abrasion due to normal use of the probe 1800, including theattachment and detachment of disposables. The distal ends of the liquidlight guides 1911, 1912, 1913, 1914, 1915, 1916 and 1917 abut againstthe optical element 1824, which illustratively is spaced 1 inch (2.5 cm)from the distal end of the lens system 1848 and 3.9 inches (10 cm) fromthe optical window 1802. The distal end surfaces of the liquid lightguides 1911, 1912, 1913, 1914, 1915, 1916 and 1917 may be generallyparallel to the surface of the optical element 1824 as shown, or may beangled relative thereto by, for example, bending the distal ends of theliquid light guides 1911, 1912, 1913, 1914, 1915, 1916 and 1917, or bygrinding and polishing the ends of the slugs therein. A protectivewindow (not shown) may be placed over the recessed end of the lenssystem 1848 flush with the distal ends of the liquid light guides 1911,1912, 1913, 1914, 1915, 1916 and 1917; alternatively, the lens system1848 may be designed to have its distal end flush with the liquid lightguides 1911, 1912, 1913, 1914, 1915, 1916 and 1917.

[0087] Although the spacing of the liquid light guides 1911, 1912, 1913,1914, 1915, 1916 and 1917 is much greater than the spacing of theoptical fibers of the bundle 340 in the probe 300, the liquid lightguides 1911, 1912, 1913, 1914, 1915, 1916 and 1917 have a significantlylarger numerical aperture, on the order of 0.5 NA compared to 0.28 NA,so that the cones of light emitted from their distal end spread outwidely, intersecting with one another as well as with the spatial mixercontained in the probe distal section 1810 essentially as occurs withthe optical fibers of the bundle 340 in the probe 300.

[0088] Although the number of liquid light guides arranged at the distalend of the reusable section 1840 of the optical probe 1800 is notcritical, the preference for dense packing of the proximal ends of theliquid light guides to improve the coupling efficiency of the lightgenerally dictates the number. Dense packing is achieved with sevenlight guides, nineteen is liquid light guides, and so forth.

[0089] Another technique for emitting light from discrete light emittingareas as many merging cones is the use of light emitting diodes (“LED”);for example, substitution of a ring of LEDs for a ring of fiber opticsor liquid light guides. The light emitting areas of the LEDs may ifdesired be oriented in generally the same way as the light emittingareas of fiber optics bundles. The use of LEDs in place of the fiberoptics bundles of the irradiator shown in FIGS. 3 and 4, or in place ofthe liquid light guides of the multiple light guide irradiator shown inFIG. 20 has the advantage of substituting electrical conductors forliquid light guides or fiber optics channeled in the conduit 1858, sothat the conduit 1858 may be made of a reduced diameter and withincreased flexibility. While LEDs of a diameter comparable with thediameter of liquid light guides or fiber optics bundles presentlyoperated at limited wavelengths, LEDs capable of operation over manydifferent wavelengths are being developed and would be suitable for usein optical probes when available.

[0090] The fiber optics irradiator shown in FIGS. 3 and 4, theirradiator shown in FIG. 10 having a single light guide 1020 which maybe implemented in a number of ways such as indicated by the embodimentsof FIGS. 14-16 and FIGS. 17-19, and the multiple light guide irradiatorshown in FIG. 20 all have their light emitting areas arranged in acircle about the axis of light collection. However, not only may lightemitting areas be arranged about the axis of light collection in avariety of geometric shapes in addition to circular, including oval,elliptic, “C” sections, free form sections, triangular, rectangular,hexagonal, octagonal, other multiple facet geometries, and anycombination of the foregoing, but a number of other parameters may bevaried for each individual light emitting area to realize the desireddegrees of diffusivity and uniformity at the optical window of theprobe. These parameters include the orientation of each of the lightemitting areas relative to the optical window and/or the spatial mixer,the spacing of the various light emitting areas from their nearestneighbors, the numeric apertures of the various light emitting areas,and the power of the light from the various light emitting areas.Moreover, the geometric shape defined by the arrangement of lightemitting areas need not be centered on or perpendicular to the axis oflight collection, provided that the desired degrees of uniformity anddiffusivity of light is realized at the optical window of the probe.

Disposables

[0091] A disposable 910 (FIG. 9) suitable for use with the reusableprobe section 900 is generally elongated for mounting to the distalextension of the probe 900 and for protecting it from contamination fromthe target and surrounding materials, and contains an inside surfacesuitable for the spatial mixing of light and an optical element. Theelongated portion of the disposable 910 may be rigid, pliable, or acombination of rigid and pliable sections, and may be made of variousmaterials such as medical grade paper, plastic, synthetic rubber,aluminum, stainless steel, laminate, and other appropriate materials.The optical element may be a rigid or pliable body, including a solidflat optical window, a sheet of pliable material, a shaped lens, aconformal window such as a window having a nipple shaped to conform tothe Os of the cervix, a fluid filled sac, or a combination thereof, andmay be made of various materials such as plastic, fused silica, glass,quartz, and other appropriate materials. The spatial mixing surface maybe a treated or coated inside surface of the elongated portion of thedisposable, or may be another type of material or materials lining orembedded in the inside surface of the elongated portion of thedisposable. For example, where the elongated portion of the disposableis a tube of extruded aluminum, the spatial mixing surface is formed bytreating the inside surface of one end of the extruded aluminum tubewith an acid etch and followed by anodization to create a light mixingsurface. Alternatively, aluminum foil having a suitable spatial mixingsurface may be applied to any suitable tube material. As used herein,“tube” refers to an elongated hollow shape of any desired cross section,including round, oval, elliptic, triangular, rectangular, other multiplefacet geometries, “C” sections, free form sections, and any combinationof the foregoing, whether varying or constant along the direction ofelongation.

[0092] The material or materials used in the disposable 910 to protectthe reusable probe section 900 from contamination constitute a fluidbarrier, which is impervious to fluids typically found at the targetsite or that impedes such fluids throughout the intended period of useof the disposable. For example, materials suitable for medicalapplications include materials, that are impervious to mammalian bodyfluids, such as aluminum, plastic, fused silica, glass, and quartz, aswell as materials that impede mammalian body fluids, such as medicalgrade paper.

[0093] FIGS. 24-27 show various disposables that include medical gradepaper in their manufacture. FIG. 24 shows a disposable 2000 thatincludes a tubular member 2002 of stiff medical grade paper which isfitted over a molded plastic base 2008. The thickness of the tube 2002depends on its length, with a tube thickness on the order of 1.3 mm(fifty thousandths of an inch) being suitable for lengths required forcervical examination. The tube 2002 is connected to the base 2008 usingany suitable technique, such as fixed with adhesive or press-fit. Thebase 2008 contains suitable connectors 2010 for connecting to thereusable optical probe section 900. A spatial mixer surface 2004 isprovided by preferably aluminum foil paper that is applied to the insideof the paper tube 2002. A suitable aluminum foil paper is made of analuminum foil liner about 0.01 mm (0.0003 inches) thick, for example,glued to 20 lb. natural Kraft backing paper, which is available fromCustom Paper Tubes, Inc. of Cleveland, Ohio. Other aluminum foil papersare also commonly available with differing paper weights and foil typesand thicknesses. For example, gold and nickel foils may be suitable invarious applications depending on the irradiation wavelengths used. Thealuminum foil paper is wound to achieve any desired internal seam.However, a spiral seam is preferred to a straight seam because a spiralseam tends to average any scattering and/or fluorescence that may begenerated by the seam over the circumference of the spatial mixer tokeep the intensity thereof below the detection threshold of the probe900. The lens 2006 is threaded on its edge and is screwed into placefrom the back of the tube 2002 prior to connecting the tube 2002 to thebase 2008. Other techniques for fitting the lens 2006 to the tube 2002include press-fitting the lens 2006 into place, gluing the lens 2006into place with a suitable adhesive, crimping the tube 2002 on bothsides of the lens 2006, providing an annular trough on the edge of thelens 2006 and crimping the tube 2002 into the trough to engage the lens2006, and so forth. Illustratively, the tube 2002 is about 10.2 cm (4inches) long, the base 2008 is about 7.6 cm (3 inches) long, and thelens 2006 is UV acrylic or equivalent.

[0094]FIG. 25 shows a disposable 2100 that includes a tubular member2102 of stiff medical grade paper with an internal spatial mixingsurface 2104. A lens 2106 is pushed into place against a crimp or othertype of retainer in the tube 2102, and the tube 2102 is pushed over amolded plastic base 2108 containing suitable connectors 2110. The moldedplastic base 2108 presses against the lens 2106, firmly seating itagainst the crimp in the tube 2102.

[0095]FIG. 26 shows a disposable 2200 that includes a tubular member2202 of stiff medical grade paper with an internal spatial mixingsurface 2204. A lens 2206 is press-fitted in proper alignment into abase 2208 or secured with adhesive, and the base 2208 is pushed into thetube 2202 and secured with a suitable adhesive.

[0096]FIG. 27 shows a disposable 2300 having a lens 2306 mounted on thedistal end thereof. The disposable 2300 includes a tubular member 2302of stiff medical grade paper with an internal spatial mixing surface2304. The tubular member 2302 is fitted over a molded plastic base 2308containing suitable connectors 2310. A lens 2306 is mounted on thedistal end of the disposable 2300 by screwing it into place or by usingany other suitable technique such as press-fitting the lens 2306 intoplace, gluing the lens 2306 into place with a suitable adhesive, orcrimping the tube 2002 to secure the lens 2306.

[0097] The various molded bases 2008, 2108, 2208 and 2308 shown in FIGS.24-27 may be molded with a flare, if desired or if necessary toaccommodate elements of the reusable probe section 900. Other materialsand manufacturing techniques may be used instead of the various moldedplastic bases 2008, 2108, 2208 and 2308; for example, extruded aluminummay be used.

[0098]FIGS. 28 and 30 show disposables 2500 and 2600 which are based onplastic tubular bodies having inside surfaces that are suitable forspatial mixing without the application of additional material ortreatments. Preferably, the plastic used for the tubular bodies of thedisposables 2500 and 2600 is an opaque, white, and substantiallynon-fluorescing material. The disposables 2500 and 2600 also includeoptical elements mounted within the tubular bodies to protect reusableprobe sections from contamination.

[0099] As is so for the other disposables described herein, thedisposables 2500 and 2600 may be fabricated for use with a variety ofdifferent reusable probe sections having different types of irradiators,since their inside spatial mixing surfaces can be tailored withincertain limits to achieve the desired balance of reflection efficiencyon the one hand and uniformity and diffusivity on the other hand. Forexample, because the light guides 1911, 1912, 1913, 1914, 1915, 1916 and1917 used in one embodiment of the reusable probe section 1840 (FIG. 20)do not provide a particularly uniform ring source, a good deal of mixingis needed to obtain the desired diffuse light in the vicinity of theoptical window 1802, even at the expense of transmission efficiency. Asurface finish greater than about 4 microinches (0.1 micrometers) and ashigh as about 63 microinches (1.6 micrometers) is appropriate when thering source is not uniform. This amount of surface roughness can befound in certain extruded plastics and can be formed as desired inmolded plastic components.

[0100] As is so for the other disposables described herein, the opticalelements of the disposables 2500 and 2600 may be positioned as desired.However, preferably the optical elements of the disposables 2500 and2600 are positioned to abut the ring light source during use, so thatthe reflected image of the ring light source is outside of the field ofview of the lens system.

[0101]FIG. 28 is a cross-sectional view of an illustrative disposable2500 for use in examining the human cervix. Connection to the reusableprobe section is by friction or pressure fit or by clamping. Thedisposable 2500 includes an optical element 2520, which may have anysuitable surface contour, illustratively flat in the disposable 2500.The material of the optical element 2520 is non-toxic. In anillustrative fabrication technique, the optical element 2520 is gluedinto place between a distal tube 2510 and a proximal tube 2530 with asuitable medical grade adhesive that is both non-toxic and acts as afluid barrier. One of the tubes, here the proximal tube 2530, has arecessed portion of the interior wall in which the optical element 2520is seated. The other tube, here the distal tube 2510, has a recessedportion of the outer wall which mates with the inside recessed portionof the proximal tube 2530 and presses against the optical element 2520to ensure proper seating thereof.

[0102] The proximal tube 2530 illustratively is 1.54 inches (3.9 cm)long and has an inside diameter of 1.000±0.015 inches (25.4 mm±0.4 mm)and a wall thickness of from 0.045 to 0.050 inches (1.14 mm to 1.27 mm).The inside wall at one end of the proximal tube 2530 is recessed in anysuitable manner to increase its inside diameter to 1.05 inches (26.7 mm)for a depth along the tube of 0.175 inches (4.45 mm). The distal tube2510 illustratively is 4.45 inches (11.3 cm) long and has an insidediameter of 1.000±0.015 inches (25.4 mm±0.4 mm) and a wall thickness offrom 0.045 to 0.050 inches (1.14 mm to 1.27 mm). The outside wall at oneend of the distal tube 2510 is recessed in any suitable manner todecrease its outside diameter to 1.04 inches (26.4 mm) for a depth alongthe tube of 0.135 inches (3.43 mm). The assembled length of thedisposable 2500 is 5.85 inches (14.86 cm).

[0103] A suitable material for the distal tube 2510 and the proximaltube 2530 is CYREX 200-8005 acrylic-polycarbonate alloy, which isavailable from CYRO Industries of Rockaway, N.J. The material isavailable in medical grade nontoxic pellets. An illustrative fabricationtechnique is to extrude the tubes using well known techniques. Theextrusion process is controlled so that the roughness of the insidesurface is on the order of 8 microinches (0.2 micrometers), which issuitable for a white plastic disposable intended for use with thereusable probe section 1840 (FIG. 20). The extruded tube is cut to thedesired dimensions, and the recesses are formed in the outside andinside walls of the distal tube 2510 and the proximal tube 2530 distaltube tubes using any suitable technique such as lathe turning, which iswell known in the art.

[0104] The optical element 2520 preferably is stamped or cut from asheet of ACRYLITE FF OP-1 clear acrylic sheet, which is available fromCYRO Industries, Inc. of Rockaway, N.J. The ACRYLITE FF OP-1 materialtransmits radiation in the wavelength range starting from about 250 nm,and in particular is capable of transmitting ultraviolet radiation. TheACRYLITE FF OP-1 material does not contain any UV stabilizers, heatstabilizers, or release agents. An acrylic free of additives isdesirable in the disposable 2500 because of the possible toxicity ofadditives in medical applications. The optical element 2520 may have anydesired antireflective (“A/R”) coating on either surface or on bothsurfaces, and any optical characteristics as may be required by the lenssystem with which it is intended for use.

[0105] Illustratively, the optical element 2520 is from 0.040 to 0.070inches (from 1 mm to 1.8) thick. The edges may be left sharp but are tobe free of burrs, and free edge chips are not to extend radially inwardmore than 0.010 inches (0.25 mm). The diameter of the optical element2520 is from 1.047 to 1.050 inches (26.59 to 26.67 mm). The acrylicsheet from which the optical element 2520 is obtained should beprotected during processing on both sides with a suitable material suchas paper. Where an anti-fog coating is used, the paper is removed fromone side of the acrylic sheet prior to application of the anti-fogcoating, and is removed from the other side of the optical element 2520prior to assembly and gluing of the disposable 2500.

[0106] The optical element 2520 preferably is coated with an anti-fogcoating on the surface facing the target to prevent fogging of theoptical element 2520 during a cervical examination. The anti-fog coatingis non-toxic and preferably clear to avoid attenuating light transmittedthrough the optical element 2520. An anti-fog coating preferably is alsoapplied to the inside surface of the distal tube 2510, either partiallyor entirely. As a hydrophilic material, the anti-fog coating tends toprevent the formation of droplets on the inside surface of the distaltube 2510, which would tend to excessively attenuate any lightencountering the droplets. Preferably, the anti-fog coating is appliedto one side of the optical element 2520 and to the proximal half of theinside surface of the distal tube 2510 prior to assembly, using anysuitable technique such as dipping or spraying. A suitable coatingmaterial and services for applying the coating material are availablefrom Hydromer, Inc. of Somerville, N.J., under the product designationHydromer 20M. Anti-fog coatings are also described in U.S. Pat. No.4,467,073 and U.S. Pat. No. 4,642,267, which hereby are incorporatedherein by reference thereto in their entirety.

[0107] A suitable material for the adhesive is EPO-TEK 301-2, which isavailable from Epoxy Technology, Inc. of Billerica, Mass. The EPO-TEK301-2 adhesive is a two component epoxy that can be cured with orwithout heat. It is an optically transparent epoxy that has lowviscosity, long pot life and good handling characteristics. It issuitable for bonding glass, quartz, metals and most plastics. The tubes2510 and 2530 and the optical element 2520 are joined by applying a thincoating of adhesive to the mating surfaces of the tubes 2510 and 2530,inserting the optical element 2520 into the mating end of the tube 2530,and inserting the mating end of the tube 2510 into the mating end of thetube 2530. The EPO-TEK 301-2 adhesive preferably is cured at 90 degreesCentigrade.

[0108] After assembly, the adhesive forms adhesive fillets 2540, 2550,2560 and 2570, which ensure that that the disposable 2500 forms aneffective fluid barrier between the target and the reusable probesection on which the disposable 2500 is mounted. Adhesive fillets 2540,2560 and 2570 should be smooth, with adjoining tube surfaces free ofadhesive film. The adhesive fillet 2540 fills a joint, the width ofwhich varies from zero to 0.025 inches (0.6 mm) depending on thethickness of the optical element 2520. The radius on window adhesivefillets should be under 0.020 inches (0.5 mm).

[0109]FIG. 30 is a cross-sectional view of an illustrative disposable2600 for use in examining the human cervix. The disposable 2600 includesa generally cylindrical and elongated tube 2610 having, for example, aflared portion and a number of tabs at its proximal end—tabs 2642 and2644 being representative—which are part of a tab and slot typeconnector. The disposable 2600 also includes optical element 2620, whichin an illustrative fabrication technique is glued into place inside ofan annular slotted rim feature 2630 with a suitable medical gradeadhesive that is both non-toxic and acts as a fluid barrier. The opticalelement 2620 may have any suitable surface contour, illustratively flatin the disposable 2600, and is coated with an anti-fog coating at leaston the surface facing the target to prevent fogging of the opticalelement 2620 during use in a cervical examination. The material of theoptical element 2620 and the anti-fog coating are non-toxic. Thedisposable 2600 has an overall length of 6.25 inches (15.9 cm), aninside diameter of 1.000±0.015 inches (25.4 mm±0.4 mm), and a wallthickness of from 0.045 to 0.050 inches (1.14 mm to 1.27 mm).

[0110] In an illustrative manufacturing technique, the tube 2610 ismolded in two halves 2612 and 2614 using well known molding techniques,and the two halves are joined together. Various features of the tube2610 such as, for example, the slotted rim feature 2630, the flaredproximal end, and the tabs 2642 and 2644, are all included in the mold.A variety of joining techniques may be used, including, for example,various adhesives, ultrasonic welding, and so forth. A suitable materialfor the tube halves 2612 and 2614 is CYREX 200-8005acrylic-polycarbonate alloy, which is available from CYRO Industries ofRockaway, N.J. The material is available in medical grade nontoxicpellets. Illustratively, the optical element 2620 is made in the samemanner as the optical element 2520, and a suitable adhesive is EPO-TEK301-2, which is available from Epoxy Technology, Inc. of Billerica,Mass.

[0111] The roughness of the inside surface of the tube halves, 2612 and2614 is determined by the surface roughness of the corresponding part ofthe mold. The use of a mold makes possible a great variety of spatialmixing, including not only wide choice in inside surface roughness butalso patterning the inside surface with differently finished regions asdesired, including regions of different roughness as well asnear-specular. For use with the probe reusable section 1840 (FIG. 20), asuitable roughness of the inside surface from at least the slotted rimfeature 2630 to the distal end is on the order of 8 microinches (0.2micrometers).

[0112] It will be appreciated that the disposables 2500 and 2600 may beformed with a flare or other deviations from cylindrical as desired oras necessary to accommodate elements of the reusable probe section.Other plastic materials, similar plastic materials with differentadditives, and different manufacturing, assembly and joining techniquesmay be substituted for the specific materials and techniques describedherein, provided that the substituted materials have similar propertiesor achieve other desired results.

[0113]FIG. 31 shows an optical probe that has a fully reusable section2400 and a disposable section 2410. The reusable section 2400 is similarto the optical probe 300, but includes a suitable connector component2420 to engage a suitable connector component (not shown) on thedisposable 2410 to hold the disposable 2410 in place in proper alignmentwith the reusable section 2400. It will be appreciated that variousother light conductors, spatial mixers, and light collectors asdescribed herein may be used instead of the fiber optics from the bundle340, the mixer 304, and the lens system 320 shown in FIG. 31. Thedisposable 2410 does not contain a spatial mixer, which is part of thereusable section 2400 as shown by reference numeral 304. However, thedisposable 2410 does include a protective elongated section,illustratively a flared tube 2412, and a protective optical window 2414,and is otherwise similar in construction and materials to the disposable910. Suitable disposables are also described in U.S. patent applicationSer. No. 08/823,044 entitled “Method and Apparatus for Calibrating anOptical Probe,” which was filed Mar. 21, 1997 and names Peter McHenryand Arthur E. Schulze as inventors, and in U.S. patent application Ser.No. 09/027,403 entitled “Contact Window Having a Tilt Characteristic forOptical Probe,” which was filed Feb. 20, 1998 and names Curtis K.Deckert as inventor, which hereby are incorporated herein in theirentirety by reference thereto.

[0114] While the specific embodiments described herein are suitable forexaminations of the human cervix, the invention is suitable for othertissue analysis by changing probe front optical-mechanicalconfiguration, excitation wavelengths from the light source, detectionwavelengths in the light detector, and diagnostic and control softwareon the computer. The probe size is scalable to function in differentways to analyze a wide variety of materials, including a variety oftissues. Any area of a body can be examined by applying a probe of theproper length with the necessary field of view, along with the propermodular changes to adjust the effective field of view. This techniquecan also be extended by the use of a flexible fiber optics interface toreach far into the body for visual examination and treatment.

[0115] While the specific embodiments of the spatial mixer describedherein use a single finish or material to achieve adequate spatialmixing for many applications, some applications may call for an unusualtype of spatial mixing. The type of spatial mixing may be varied byproviding a variety of surface finishes or materials on the inside wallof the spatial mixer to optimize spatial mixing and/or regions ofirradiation for a particular application. For example, in onearrangement (not shown) a cylindrical segment of the inside wall of thespatial mixer nearest the light source is a specular or reflectingsurface, the middle cylindrical segment is a diffuse or scatteringsurface, and the last cylindrical segment nearest the distal end of theprobe is an absorber. The absorber section may be eliminated where thefield of view of the lens system is appropriately limited. Many suitablematerials, finishes, and geometries are well-known to those of ordinaryskill in the art to achieve a specular, diffuse or absorbing surface, asdesired.

[0116] While many of the embodiments described herein include variousvalues and dimensions, these are illustrative and other values anddimensions may also be useful. For example, the number, groupings, andsize of the fibers in the irradiation system are illustrative.

What is claimed is:
 1. An optical probe having a distally disposedoptical window, comprising: a light collector having an axis of lightcollection passing through the optical window and a focal planegenerally proximate the optical window; a light source having a lightprojection pattern about the axis of light collection; and a spatialmixer having a proximal end in optical communication with the lightsource, a distal end in optical communication with the optical window,and an axis of light projection passing through the optical window, thespatial mixer further having a light mixing surface partiallyintersected by the light projection pattern of the light source toestablish a distribution of irradiation ray angles proximate the opticalwindow that has a maximum away from normal and near-normal to the axisof light projection.
 2. An optical probe as in claim 1 wherein the axisof light collection and the axis of light projection are coaxial at theoptical window.
 3. An optical probe as in claim 2 wherein the axis oflight collection and the axis of light projection are coaxial throughthe spatial mixer.
 4. An optical probe as in claim 1 further comprisinga unitary body having a distal end containing the optical window and aproximate end, the light collector, the light source, and the spatialmixer being mounted to the body.
 5. An optical probe as in claim 4further comprising a handle coupled to the body near the proximal endthereof.
 6. An optical probe as in claim 1 further comprising a bodyhaving a proximal section and a distal section containing the opticalwindow.
 7. An optical probe as in claim 6 further comprising a handlecoupled to the proximal body section.
 8. An optical probe as in claim 6wherein the distal body section is removably coupled to the proximalbody section.
 9. An optical probe as in claim 8 wherein the distal bodysection is reusable.
 10. An optical probe as in claim 8 wherein thedistal body section is disposable.
 11. An optical probe as in claim 10wherein the spatial mixer is mounted to the distal body section and thelight collector and the light source are mounted to the proximal bodysection.
 12. An optical probe as in claim 10 wherein the lightcollector, the light source, and the spatial mixer are mounted to theproximal body section.
 13. An optical probe as in claim 10 wherein thedistal section is single use.
 14. An optical probe as in claim 1 whereinthe optical window is an opening in a distal end of the optical probe.15. An optical probe as in claim 14 wherein the axis of light collectionpasses through the spatial mixer, further comprising an optical elementdisposed in the spatial mixer along the axis of light collection.
 16. Anoptical probe as in claim 14 wherein the axis of light collection passesthrough the spatial mixer, further comprising an optical elementdisposed in the spatial mixer near the proximal end thereof and alongthe axis of light collection.
 17. An optical probe as in claim 1 furthercomprising an optical element disposed in the optical window.
 18. Anoptical probe as in claim 17 wherein the optical element is a flat rigidwindow.
 19. An optical probe as in claim 17 wherein the optical elementis a shaped lens.
 20. An optical probe as in claim 17 wherein theoptical element comprises a surface contoured to generally conform withthe surface of a human cervix.
 21. An optical probe as in claim 17wherein the axis of light collection passes through the spatial mixer,further comprising another optical element disposed in the spatial mixeralong the axis of light collection.
 22. An optical probe as in claim 17wherein the axis of light collection passes through the spatial mixer,further comprising another optical element disposed in the spatial mixernear the proximal end thereof and along the axis of light collection.23. An optical probe as in claim 1 wherein the light collectorcomprises: a telecentric lens system; and a fiber optics bundle coupledto the telecentric lens system for carrying an image from thetelecentric lens system to an external detector.
 24. An optical probe asin claim 1 wherein the light collector comprises: a near-telecentriclens system; and a fiber optics bundle coupled to the near-telecentriclens system for carrying an image from the near-telecentric lens systemto an external detector.
 25. An optical probe as in claim 1 wherein thelight collector comprises: a non-telecentric lens system; and means forcorrecting the non-telecentric lens system for non-uniformity across thefield of view of the optical probe.
 26. An optical probe as in claim 1wherein the light collector comprises a lens system, the optical probefurther comprising a light detector optically coupled to the lenssystem.
 27. An optical probe as in claim 26 wherein the light detectorcomprises a CCD camera.
 28. An optical probe as in claim 1 wherein thelight collector has a field of view that excludes the mixing surface ofthe spatial mixer and includes substantially the entire area of theoptical window.
 29. An optical probe as in claim 1 wherein the focalplane of the light collector is distal to the optical window.
 30. Anoptical probe as in claim 1 wherein the focal plane of the lightcollector is proximal to the optical window.
 31. An optical probe as inclaim 1 wherein the light source comprises a plurality of optical fibersarranged on all sides of the light collector, each of the fibers havingan optical axis directed toward the optical window.
 32. An optical probeas in claim 1 wherein the light source comprises a light guide arrangedon all sides of the light collector, the light guide projecting lightgenerally toward the optical window.
 33. An optical probe as in claim 1wherein the light source comprises a plurality of light guides arrangeda bout the light collector.
 34. An optical probe as in claim 33 whereinthe light guides have respective optical axes directed toward theoptical window.
 35. An optical probe as in claim 1 wherein the lightsource comprises a plurality of optical fibers arranged about the lightcollector.
 36. An optical probe as in claim 35 wherein the opticalfibers have respective optical axes directed toward the optical window.37. An optical probe as in claim 1 wherein the light source comprises aplurality of light emitting diodes arranged about the light collector.38. An optical probe as in claim 37 wherein the light emitting diodeshave respective optical axes directed toward the optical window.
 39. Anoptical probe as in claim 1 wherein the light projection pattern of thelight source partially intersects the light mixing surface to establisha distribution of ray angles proximate the optical window that has amaximum near-parallel to the axis of light projection.
 40. An opticalprobe as in claim 1 wherein the mixing surface comprises a lightscattering surface.
 41. An optical probe as in claim 1 wherein themixing surface comprises a light scattering surface in combination witha specular surface over respective areas of the mixing surface.
 42. Anoptical probe as in claim 1 wherein the mixing surface comprises a lightscattering surface in combination with a light absorbing surface overrespective areas of the mixing surface.
 43. An optical probe as in claim1 wherein the mixing surface comprises a light scattering surface incombination with a specular surface and a light absorbing surface overrespective areas of the mixing surface.
 44. An optical probe as in claim1 wherein the mixing surface comprises a metallic foil.
 45. An opticalprobe as in claim 1 wherein the mixing surface comprises a plastichaving a surface finish in the range of about 4 microinches to about 63microinches.
 46. An optical probe as in claim 1 wherein the lightprojection pattern is a ring.
 47. An optical probe as in claim 1 whereinthe light projection pattern is an ellipse.
 48. An optical probe as inclaim 1 wherein the light projection pattern is a triangle.
 49. Anoptical probe for examining, through an optical window therein, livingtissue in the interior of cavities having restricted access throughorifices or passageways, comprising: a body having an elongated distalsection containing the optical window, and a proximal section; a lenssystem mounted in the body, the lens system having an optical axispassing through the optical window of the probe and a focal plane lyinggenerally proximate to the optical window; a light source mounted in thebody about the lens system, the light source being coaxial with the lenssystem and having a direction of light projection generally toward theoptical window; and an elongated inside surface having one end disposedgenerally about the light source and another end disposed generallyabout the optical window, the inside surface comprising a lightscattering surface and the light projection at least partiallyintersecting the light scattering surface to establish a distribution ofray angles proximate the optical window that has a maximum near-parallelto the optical axis of the lens system.
 50. An optical probe as in claim49 further comprising a lens mounted to the distal section along theoptical axis of the lens system and at the optical window, wherein thelens system in combination with the lens is a telecentric lens system.51. An optical probe as in claim 49 further comprising a lens mounted tothe distal section along the optical axis of the lens system.
 52. Anoptical probe as in claim 49 wherein the light source is a ringirradiator.
 53. An optical probe as in claim 52 wherein the ringirradiator comprises a plurality of optical fibers arranged in a ring.54. An optical probe as in claim 52 wherein the ring irradiatorcomprises a cylindrical light guide.
 55. An optical probe as in claim 52wherein the ring irradiator comprises a plurality of light guidesarranged in a ring.
 56. An optical probe having a distally disposedoptical window, comprising: a light collector having an axis of lightcollection passing through the optical window and a focal planegenerally proximate the optical window; a light source having aplurality of light emitting areas disposed about the axis of lightcollection; and a spatial mixer having a proximal end in opticalcommunication with the light source and a distal end in opticalcommunication with the optical window to establish a direction of lightprojection generally toward the optical window and generally along atleast part of the axis of light collection, the spatial mixer furtherhaving a light mixing surface at least partially intersected by rays oflight from the light emitting areas to establish a diffuse lightproximate the optical window having a distribution of irradiation rayangles that has a maximum away from normal and near-normal to thedirection of light projection.
 57. An optical probe as in claim 56wherein the plurality of light emitting areas of the light source aremerged about the axis of light collection.
 58. An optical probe as inclaim 57 wherein the plurality of light emitting areas of the lightsource are disposed about the axis of light collection in a ringcentered on the axis of light collection.
 59. An optical probe as inclaim 57 wherein: the light collector comprises a periphery generallyparallel to the axis of collection; and the light source comprises aliquid light guide having a distal end directed generally toward theoptical window and a portion in proximity to the distal end disposedgenerally throughout the periphery of the light collector.
 60. Anoptical probe as in claim 56 wherein the plurality of light emittingareas of the light source are discretely disposed about the axis oflight collection.
 61. An optical probe as in claim 60 wherein theplurality of light emitting areas of the light source are disposed aboutthe axis of light collection in a ring centered on the axis of lightcollection.
 62. An optical probe as in claim 61 wherein the lightemitting areas emit light in a cone.
 63. An optical probe as in claim 60wherein: the light collector comprises a periphery generally parallel tothe axis of collection; and the light source comprises a plurality ofoptical fibers having respective distal ends directed generally towardthe optical window and respective lengths in proximity to the endsdisposed generally at the periphery of the light collector.
 64. Anoptical probe as in claim 60 wherein: the light collector comprises aperiphery generally parallel to the axis of collection; and the lightsource comprises a plurality of light guides having respective distalends directed generally toward the optical window and respective lengthsin proximity to the ends disposed generally at the periphery of thelight collector.
 65. An optical probe as in claim 56 wherein theplurality of light emitting areas of the light source are disposed aboutthe axis of light collection in a ring.
 66. An optical probe as in claim56 wherein the plurality of light emitting areas of the light source aredisposed about the axis of light collection in an ellipse.
 67. Anoptical probe as in claim 56 wherein the plurality of light emittingareas of the light source are disposed about the axis of lightcollection in a triangle.
 68. An optical probe as in claim 56 whereinthe axis of light collection and the direction of light projection arecoaxial at the optical window.
 69. An optical probe as in claim 68wherein the axis of light collection and the direction of lightprojection are coaxial through the spatial mixer.
 70. An optical probeas in claim 56 wherein the rays of light from the light source thatintersect the light mixing surface establish, along with direct rays oflight from the light source, a diffuse light proximate the opticalwindow having a distribution of ray angles that has a maximumnear-parallel to the direction of light projection.
 71. An optical probeas in claim 56 further comprising a reusable body containing the lightcollector, the light source, the optical window, and the spatial mixer.72. An optical probe as in claim 56 further comprising: a reusableproximal body section containing the light collector and the lightsource; and a disposable distal section removably coupled to theproximal body section and containing the optical window and the spatialmixer.
 73. An optical probe as in claim 72 wherein the optical elementis disposed in proximity to the light emitting areas of the light sourceand recessed from the distal end of the disposable distal section. 74.An optical probe as in claim 73 wherein the disposable distal sectioncomprises a plastic tube.
 75. An optical probe as in claim 74 whereinthe spatial mixer comprises an interior surface of the plastic tubedisposed at least partially between the optical element and the opticalwindow.
 76. An optical probe as in claim 75 wherein the spatial mixerhas a surface finish in the range of about 4 microinches to about 63microinches.
 77. An optical probe as in claim 76 wherein the opticalelement comprises an anti-fog coating on at least a surface facing theoptical window.
 78. An optical probe as in claim 77 wherein the spatialmixer comprises an anti-fog coating on at least a portion thereofbetween the optical element and the optical window.
 79. An optical probeas in claim 56 wherein the light collector has a field of view thatexcludes substantially the entire spatial mixer and includessubstantially the entire area of the optical window.
 80. An opticalprobe as in claim 79 wherein the light collector has a focal planedistal of the optical window.
 81. An optical probe as in claim 79wherein the light collector has a focal plane proximal of the opticalwindow.
 82. An optical probe as in claim 79 wherein the light collectorhas a focal plane at the optical window.
 83. An optical probe as inclaim 56 wherein the light collector comprises: a lens system; and anoptical transmission medium coupled to the lens system and extending toan external detector.
 84. An optical probe as in claim 56 wherein thelight collector comprises a lens system, the optical probe furthercomprising a light detector optically coupled to the lens system.
 85. Anoptical probe as in claim 84 wherein the light detector comprises a CCDcamera.
 86. A disposable for an optical probe, the disposable having adistal end to contact a target having a fluid associated therewith and aproximal end to mount to a reusable optical probe section, thedisposable comprising: a body having a mounting surface toward theproximal end and a light mixing inside surface toward the distal end;and an optical window element disposed within the body, the opticalwindow element and the body proximal of the optical window element beingbarriers to the fluid.
 87. A disposable as in claim 86 wherein the bodycomprises a tube and the light mixing inside surface comprises ametallic foil disposed on the inside of the tube.
 88. A disposable as inclaim 87 wherein the tube is paper.
 89. A disposable as in claim 87wherein the tube is plastic.
 90. A disposable as in claim 87 wherein thetube is extruded aluminum.
 91. A disposable as in claim 86 wherein thebody comprises an extruded aluminum tube and the light mixing insidesurface comprises an inside surface of the extruded aluminum tube havinga light scattering surface treatment.
 92. A disposable as in claim 86wherein the body comprises a tube and the light mixing inside surfacecomprises a liner having a light scattering property disposed on theinside of the tube.
 93. A disposable as in claim 86 wherein the bodycomprises a tube and the light mixing inside surface comprises an insidesurface of the tube having a light scattering treatment.
 94. Adisposable as in claim 86 wherein the body comprises a tube and themounting surface comprises a mechanical connector integral with thetube.
 95. A disposable as in claim 94 wherein the tube is paper.
 96. Adisposable as in claim 94 wherein the tube is plastic.
 97. A disposableas in claim 94 wherein the tube is extruded aluminum.
 98. A disposableas in claim 86 wherein the body comprises: a first tube, the lightmixing inside surface comprising a metallic foil disposed on the insideof the first tube; and a second tube coupled to the first tube, themounting surface comprising a mechanical connector integral with thesecond tube.
 99. A disposable as in claim 98 wherein the optical windowelement is mounted within the first tube.
 100. A disposable as in claim98 wherein the optical window element is mounted at a distal end of thefirst tube.
 101. A disposable for an optical probe, the disposablehaving a distal end to contact a target having a fluid associatedtherewith and a proximal end to mount to a reusable optical probesection, the disposable comprising: a body having an inside surfacebounding an interior space extending between the proximal end and thedistal end, the inside surface comprising at least in part a lightmixing surface; an optical element disposed across the interior space,the optical element and the body at least proximal of the opticalelement being barriers to the fluid; and a reusable optical probesection connector integrated with the body.
 102. A disposable as inclaim 101 wherein the optical element is recessed from the distal end ofthe body.
 103. A disposable as in claim 102 wherein at least part of thelight mixing surface is disposed between the optical element and thedistal end of the body.
 104. A disposable as in claim 101 wherein theoptical element is disposed at the distal end of the body.
 105. Adisposable as in claim 101 wherein the body comprises a plastic tubehaving an inside surface of a predetermined roughness surrounding atleast a part of the interior space, the spatial mixer comprising theinside surface of the plastic tube.
 106. A disposable as in claim 101wherein the body comprises a paper tube having an inside foil lining,the foil lining having an inside surface of a predetermined roughnesssurrounding at least a part of the interior space, the spatial mixercomprising the inside surface of the foil lining.
 107. A disposable asin claim 101 wherein the body comprises a metallic tube having an insidesurface of a predetermined roughness surrounding at least a part of theinterior space, the spatial mixer comprising the inside surface of themetallic tube.
 108. A disposable as in claim 101 wherein the bodycomprises at least one extruded tubular member.
 109. A disposable as inclaim 108 wherein the reusable optical probe section connector iscoupled to the extruded tubular member.
 110. A disposable as in claim101 wherein the body comprises a plurality of molded members.
 111. Adisposable as in claim 101 wherein the body comprises a plurality ofmolded members, the molded members further comprising respectiveportions of the reusable optical probe section connector.
 112. Adisposable for an optical probe, the disposable having a distal end tocontact a target having a fluid associated therewith and a proximal endto mount to a reusable optical probe section, the disposable comprising:a tubular plastic body having an inside surface bounding an interiorspace extending between the proximal end and the distal end, the insidesurface comprising at least in part a light mixing surface; an opticalelement disposed across the interior space, the optical element and thebody being barriers to the fluid; and a reusable optical probe sectionconnector integrated with the body.
 113. A disposable as in claim 112wherein the light mixing surface has a finish in the range of about 4microinches to about 63 microinches.
 114. A disposable as in claim 113wherein the body comprises an assembly of extruded plastic tubularmembers.
 115. A disposable as in claim 114 wherein the reusable opticalprobe section connector is assembled to the body.
 116. A disposable asin claim 113 wherein the body comprises an assembly of molded members.117. A disposable as in claim 116 wherein the molded members includingrespective parts of the reusable optical probe section connector.
 118. Adisposable as in claim 113 further comprising an anti-fog materialdisposed on at least a surface of the optical element facing the distalend of the disposable.
 119. A disposable as in claim 118 furthercomprising an anti-fog material disposed on at least a portion of thelight mixing surface.